AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2008
Emiko Sato
Epstein,Barr virus (EBV)-associated T/NK-cell lymphoproliferative disease (LPD) has been linked to several different disorders. Its prognosis is generally poor and a treatment strategy has yet to be established. There are reports, however, that hematopoietic stem cell transplantation (HSCT) can cure this disease. To clarify the current situation regarding allogeneic hematopoietic stem cell transplantation (allo-HSCT) for EBV-associated T/NK-LPD, a nationwide survey was performed in Japan. Data for 74 patients were collected. There were 42 cases of chronic active EBV infection (CAEBV), 10 cases of EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), and 22 cases of EBV-associated lymphoma/leukemia (EBV-lymphoma/leukemia). Of those with CAEBV, 54% had the EBV-infected T-cell type and 59% with EBV-lymphoma/leukemia had the EBV-infected NK-cell type. Most patients with EBV-HLH and EBV-lymphoma/leukemia received allo-HSCT within 1 year after onset compared to only 14% of patients with CAEBV. The event-free survival (EFS) rate following allo-HSCT was 0.561 ± 0.086 for CAEBV, 0.614 ± 0.186 for EBV-HLH, and 0.309 ± 0.107 for EBV-lymphoma/leukemia. The EFS of allo-HSCT with conventional conditioning was 0.488 ± 0.074 and with reduced-intensity conditioning was 0.563 ± 0.124. Thus, in a substantial number of cases, EBV-associated T/NK-LPD can be cured by either allogeneic conventional stem cell transplantation or reduced-intensity stem cell transplantation. © 2008 Wiley-Liss, Inc. Am. J. Hematol., 2008. [source]

Flow cytometry for ZAP-70: New colors for chronic lymphocytic leukemia

CYTOMETRY, Issue 4 2006
Adrian Wiestner
Abstract ZAP-70 has become one of the most studied prognostic markers in Chronic Lymphocytic Leukemia (CLL). ZAP-70 is remarkable in many ways: ZAP-70 has been identified as the best discriminating gene between prognostically distinct CLL subtypes using large scale gene expression profiling; ZAP-70 has been shown to enhance signal transduction in CLL B-cells and therefore could contribute to disease progression; and ZAP-70 is one of the rare examples of an intracellular target considered for clinical flow cytometry. This issue attests to the enormous effort and the steady progress made in overcoming technical challenges of testing for ZAP-70 expression and sets the foundation for a successful translation of this important marker into clinical practice. Despite the best effort, one will likely have to accept that not all cases can be clearly assigned to one or the other group, given that ZAP-70 expression between CLL patients falls along a continuum from absent to high. Nevertheless, ZAP-70 expression could become a key parameter to guide patients towards risk adapted treatment strategies in prospective clinical trials. © 2006 International Society for Analytical Cytology [source]

4th International Symposium on Leukemia and Lymphoma

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2000
Molecular Pharmacology, New Treatment Modalities
No abstract is available for this article. [source]

Hematological malignancies in the island of Sardinia, 1974,1993: age and sex distributions and temporal changes in incidence

HEMATOLOGICAL ONCOLOGY, Issue 3 2004
G. Broccia
Abstract We have collected, by an active retrospective survey, all the cases of hematologic malignancies (HM) newly diagnosed during the time period 1974,1993 in the resident population of Sardinia. Diagnosis was deemed valid, after consultation of clinical records, in more than 90% of the 7264 collected cases. The number of newly diagnosed cases by year more than doubled during the 20-year period investigated. This striking increase can be only partially accounted for by ageing of population. Indeed, age-specific and age-adjusted rates of most of HM increased during this period, although Hodgkin Disease (HD), Chronic Myeloid Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL) were notable exceptions. The observed increase in rates is likely, in a large part, to be fictitious, due to easier access to a health care system, which in the meantime, improved its diagnostic efficiency. This was particularly evident for Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM) and some others myelo- and lympho-proliferative disorders, but its relevance declined after 1984,1989. A likely true increase in occurrence was evidenced for Non-Hodgkin Lymphomas (NHL) and similarly, although to a lesser extent and more doubtful, for Myelodysplasias (MDS) and Acute Myeloid Leukemia (AML). At the end of the studied period each type of HM presented age and sex distributions and age-adjusted rates that show only minor differences from those reported for other western countries. No argument emerged to suggest that any genetic peculiarities of the Sardinian population might have affected the occurrence of HM. The confounding effects of improved diagnostic efficiency have prevented a reliable assessment of influence on incidences of environmental and socio-economic changes that, in relatively recent times, have occurred in Sardinia. Copyright © 2005 John Wiley & Sons, Ltd. [source]

An 85-Year-Old Japanese Woman with Philadelphia Chromosome,Positive Chronic Myelogenous Leukemia with Del (5q) Successfully Treated by Intermittent Imatinib Therapy

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2004
Toyoki Maeda MD
No abstract is available for this article. [source]

Cancer stem cells in leukemia, recent advances

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2007
Gang-Ming Zou
The history of stem cell research was started in the early 1900s in Europe where the researcher realized that various types of blood cells came from a particular "stem cells." However, it was not until 1963 that the first quantitative description of the self-renewal activities of transplanted mouse bone marrow cells were documented by Canadian scientist Ernest A McCulloch and James E Till in Toronto. The concept of cancer stem cells has been used over 50 years ago; whereas the strong evidence for the existence of a Cancer Stem Cells was obtained recently. Consequently, there is increasing attention in recent year about cancer stem cells. The findings from recent studies support the concept that stem cells are integral to the development of several forms of human cancer. Changes in stem cell behavior can contribute to tumor formation. Leukemia is a cancer of blood-forming tissue, including the bone marrow and lymphatic system. Leukemic stem cells represent the cancer stem cells in the leukemia. In this review, we summarize the recent advance in the study of leukemic stem cells. J. Cell. Physiol. 213: 440,444, 2007. © 2007 Wiley-Liss, Inc. [source]

Subcutaneous Panniculitis-Like T Cell Lymphoma Developing in a Patient with Chronic B-Cell Lympocytic Leukemia

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005
L Shahabi
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an unusual peripheral lymphoma most typically presenting with a cytotoxic (CD8-positive, TIA-1-positive) immunophenotype. SPTCLs may have an indolent or highly aggressive clinical course. Histologically, SPTCL may be notoriously difficult to diagnosis. Cases of SPTCL with a deceptively benign appearance similar to that of subcutaneous lupus erythematosus have been described. SPTCL associated with a concomitant systemic leukemia/lymphoma has not been documented in the literature. We report a case of SPTCL arising in a 65-year-old female with a well-established history of B-cell lymphocytic leukemia (BCLL). She presented with two months of recurrent fever and painless erythematous nodules on bilateral lower extremities that were clinically felt to be erythema nodosum. Initial biopsies demonstrated a polymorphous lobular infiltrate with neutrophils, karyorrhexis and lipomembranous change. An excisional biopsy demonstrated an atypical lymphoid population that expressed CD8 and TIA1. PCR analysis confirmed T-cell receptor gene arrangement. The patient was treated with systemic chemotherapy with resolution of her symptoms and complete remission. This is the first well documented case of SPTCL occurring in a patient with long standing B-CLL, and highlights the difficulty of establishing an unequivocal diagnosis of SPTCL. [source]

Leukemia and P32 radionuclide synovectomy for hemophilic arthropathy

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2005
A. L. DUNN
No abstract is available for this article. [source]

Immunophenotypic Classification of Leukemia in 3 Horses

JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2001
J. Trenton McClure
First page of article [source]

Successful Application of OPLS-DA for the Discrimination of Wild-Type and Mutated Cells in Acute Lymphoblastic Leukemia

MOLECULAR INFORMATICS, Issue 8 2009
Claudio, Giuseppe Molteni
Abstract OPLS-DA was successfully applied to select of a limited number of gene transcripts necessary to discriminate wild type and mutated cells in ALL patients. In the above list it was possible to identify candidate genes that could be involved in the molecular mechanisms linking PTPN11 and RAS mutations to B-ALL genesis. OPLS-DA and SIMCA classification provide a set of 50 and 77 variables respectively suitable to discriminate wild type from mutated cells in ALL patients. [source]

Infant leukemia and congenital abnormalities: A Children's Oncology Group study,

PEDIATRIC BLOOD & CANCER, Issue 1 2010
Kimberly J. Johnson PhD
Abstract Background Leukemia in infants is rare and has not been well studied apart from leukemia in older children. Differences in survival and the molecular characteristics of leukemia in infants versus older children suggest a distinct etiology, likely involving prenatal factors. Procedure We examined the association between eight categories of maternally reported congenital abnormalities (CAs) (cleft lip or palate, spina bifida or other spinal defect, large or multiple birthmarks, other chromosomal abnormalities, small head or microcephaly, rib abnormalities, urogenital abnormalities, and other) and infant leukemia in a case,control study. The study included 443 cases diagnosed at <1 year of age at a Children's Oncology Group Institution in the United States or Canada from 1996 to 2006 and 324 controls. Controls were recruited from the cases' geographic area either by random digit dialing (1999,2002) or through birth certificates (2003,2008) and were frequency-matched to cases on birth year. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression after adjustment for birth year and a measure of follow-up time to account for differences in the CA observation period. Results No statistically significant associations were observed between infant leukemia and any CA (OR,=,1.2; 95% CI: 0.8,1.9), birthmarks (OR,=,1.4; 95% CI: 0.7,2.5), urogenital abnormalities (OR,=,0.7; 95% CI: 0.2,2.0), or other CA (OR,=,1.4; 95% CI: 0.7,2.8). Results were similar for acute lymphoblastic and myeloid leukemia cases. Fewer than five subjects were in the remaining CA categories precluding analysis. Conclusions Overall, we did not find evidence to support an association between CAs and infant leukemia. Pediatr Blood Cancer 2010;55:95,99. © 2010 Wiley-Liss, Inc. [source]

Successful Treatment of Severe Iatrogenic Calcinosis Cutis with Intravenous Sodium Thiosulfate in a Child Affected by T-Acute Lymphoblastic Leukemia

PEDIATRIC DERMATOLOGY, Issue 3 2009
Colombatti Raffaella M.D., Ph.D.
We describe a 5-year-old boy with acute lymphoblastic leukemia who developed severe calcinosis cutis in the right forearm and hand, and in the left leg and foot after extravasation of calcium gluconate during treatment for tumor-lysis-syndrome-related hypocalcaemia. Surgical debridement, local wound care, hyperbaric oxygen therapy, and sodium thiosulfate infusion achieved a complete healing of all lesions in an eight-month period with a short discontinuation of chemotherapy. No functional or sensitive impairment remained. [source]

Leukemia Cutis Following Biphenotypic Congenital Leukemia

PEDIATRIC DERMATOLOGY, Issue 5 2007
ESAD KOKLU M.D.
No abstract is available for this article. [source]

Reciprocal Relationship Between a Ph-Negative Clone With Trisomy 8 Associated With Severe Myelodysplasia and a Ph-Positive Clone Following Imatinib Treatment in a Patient With Accelerated-Phase Chronic Myelogenous Leukemia (CML)

AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2004
Paulina Patchenko
No abstract is available for this article. [source]

Flow cytometric analysis of cell-surface and intracellular antigens in the diagnosis of acute leukemia

AMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2001
Rogelio Paredes-Aguilera
Abstract To evaluate the usefulness of flow cytometric detection of intracellular antigens (Ags) in establishing proper lineage affiliation and its contribution to the diagnosis of acute leukemia, we studied 100 consecutive patients in whom acute leukemia was diagnosed between January 1997 and July 1998. Immunological classification was assessed using a three-line panel of monoclonal antibodies for phenotypic characterization of leukemic blast cells as proposed at the First Latin American Consensus Conference for Flow Cytometric Immunophenotyping of Leukemia. We found 74 cases of B-cell lineage acute lymphoblastic leukemia (ALL), seven cases of T-cell ALL, and 19 cases of acute myeloid leukemia (AML). In this study cytoplasmic (cy) CD79a, cyCD22, cyCD3, and cyMPO were highly sensitive, specific B, T, and myeloid markers that were expressed in virtually all cases of B and T cell ALL and in all subtypes of AML. Applied in combination with immunophenotyping this knowledge led to improvement in diagnostic precision and refinement of immunological classification, ensuring the selection of the most appropriate therapy for the patients studied. In conclusion, intracellular Ags detection was of utmost importance in establishing correct lineage affiliation in cases lacking expression of B, T, or myeloid surface Ags or disclosing equivocal or ambiguous immunophenotypic features and in identifying biphenotypic acute leukemia. In combination with FAB morphology and immunophenotyping, we were able to reliably classify all patients with acute leukemia in this study. Am. J. Hematol. 68:69,74, 2001. © 2001 Wiley-Liss, Inc. [source]

Leukemia and exposure to ionizing radiation among German uranium miners

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 4 2006
Matthias Möhner PhD
Abstract Background It is well known that uranium miners are at an increased risk of lung cancer. Whether they also have an increased risk for other cancer sites remains under discussion. The aim of this study was to examine the leukemia risk among miners. Methods An individually matched case-control study of former uranium miners in East Germany was conducted with 377 cases and 980 controls. Results Using conditional logistic regression models, a dose,response relationship between leukemia risk and radon progeny could not be confirmed. Yet, a significantly elevated risk is seen in the category ,400 mSv when combining ,-radiation and long-lived radionuclides. Conclusions The results suggest that an elevated risk for leukemia is restricted to employees with a very long occupational career in underground uranium mining or uranium processing. Moreover, the study does not support the hypothesis of an association between exposure to short-lived radon progeny and leukemia risk. Am. J. Ind. Med. 49:238,248, 2006. © 2006 Wiley-Liss, Inc. [source]

Aetiology of childhood leukemia

BIOELECTROMAGNETICS, Issue S7 2005
Tracy Lightfoot
Abstract Leukemia is the most common cancer to affect children, accounting for approximately a third of all childhood cancers. The major morphological subtypes of leukemia, acute lymphoblastic leukemia (ALL), and acute myeloblastic leukemia (AML), are characterized by chromosomal translocations involving over 200 genes including mixed lineage leukemia (MLL), TEL, and AML1. Chromosomal translocations involving the MLL gene at 11q23 are a common feature of infant acute leukemia, found in up to 80% of all cases, and there is strong evidence that rearrangements involving the MLL gene or the TEL-AML1 gene fusion can originate in utero. As with most other cancers, the mechanism by which leukemia arises is likely to involve gene-environment interactions. Accordingly, it is important to identify exposures that cause DNA damage and induce chromosome breaks which are inadequately repaired, ultimately leading to the initiation and disease progression. Exposures acting before birth and early in life has long been thought to be important determinants of leukemia, and the list of suspected chemical, physical, and biological agents continues to increase. Unfortunately, the evidence regarding the majority of suggested exposures is limited and often contradictory, and there are areas, which clearly warrant further investigation in order to further our understanding of the aetiology of childhood leukemia. Bioelectromagnetics Supplement 7:S5,S11, 2005. © 2005 Wiley-Liss, Inc. [source]

Occupational Formaldehyde Exposure Linked to Increased Risk of Myeloid Leukemia and Death

CA: A CANCER JOURNAL FOR CLINICIANS, Issue 3 2010
John Henry Dreyfuss
No abstract is available for this article. [source]

Cord Blood Transplants Help Adults with Leukemia

CA: A CANCER JOURNAL FOR CLINICIANS, Issue 2 2005
Article first published online: 31 DEC 200
No abstract is available for this article. [source]

MUM1/IRF4 Expression Is an Unfavorable Prognostic Factor in B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

CANCER SCIENCE, Issue 6 2002
Masato Ito
B-Cell chronic lymphocytic leukemia (B-CLL)/small lymphocytic lymphoma (SLL) consists of heterogeneous diseases that are distinguished by morphological, immunophenotypic and molecular features. MUM1 (multiple myeloma oncogene 1) is a protooncogene that is deregulated as a result of (6;14)(p25;q32) chromosomal translocation in multiple myeloma, and is also expressed in a variety of malignant lymphoma entities. We examined the expression of MUM1 in B-CLL/SLL, and found that 2 of 4 B-CLL-derived cell lines and 14 of 29 patients' specimens expressed MUM1 by immunohistochemical analysis. MUM1 expression was not associated with CD38 expression, somatic hypermutation of immunoglobulin heavy chain gene variable region (IgVH), or any other clinical characteristics of the patients. Interestingly, the patients who were positive for MUM1 showed shorter overall survival tunes than those who were negative for MUM1 (50% survival: 22 months vs. 82 months) (P=0.0008, log-rank test). Multivariate analysis by Cox's proportional-hazards regression model showed that MUM1 expression and unmutated IgVH status were independent unfavorable prognostic factors in patients with B-CLL/SLL. These findings suggest that MUM1 expression is a useful prognostic factor in B-CLL/SLL. The biological role and mechanism of action of MUM1 in B-CLL/SLL need to be clarified for the development of therapies for patients with the poor prognostic subtype. [source]

Comparative QSAR Studies on Toxicity of Phenol Derivatives Using Quantum Topological Molecular Similarity Indices

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 5 2010
Bahram Hemmateenejad
Quantitative structure activity relationship (QSAR) analyses using a novel type of electronic descriptors called quantum topological molecular similarity (QTMS) indices were operated to describe and compare the mechanisms of toxicity of phenols toward five different strains (i.e., Tetrahymena pyriformis, L1210 Leukemia, Pseudomonas putida, Raja japonica and Cucumis sativus). The appropriate QSAR models for the toxicity data were obtained separately employing partial least squares (PLS) regression combined with genetic algorithms (GA), as a variable selection method. The resulting QSAR models were used to identify molecular fragments of phenol derivatives whose electronic properties contribute significantly to the observed toxicities. Using this information, it was feasible to discriminate between the mechanisms of action of phenol toxicity to the studied strains. It was found that toxicities of phenols to all strains, except with L1210 Leukemia, are significantly affected by electronic features of the phenolic hydroxyl group (C-O-H). Meanwhile, the resulting models can describe the inductive and resonance effects of substituents on various toxicities. [source]

Current Awareness in Hematological Oncology

HEMATOLOGICAL ONCOLOGY, Issue 2 2008
Article first published online: 28 MAY 200
In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of hematological oncology. Each bibliography is divided into 14 sections: 1 Reviews; 2 General; Leukemias: 3 Lymphoblastic; 4 Myeloid & Myelodysplastic Syndromes; 5 Chronic; 6 Others; Lymphomas: 7 Hodgkin's; 8 Non-Hodgkin's; 9 Plasmacytomas/Multiple Myelomas; 10 Others; 11 Bone Marrow Transplantation; 12 Cytokines; 13 Diagnosis; 14 Cytogenetics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. [source]

Current Awareness in Hematological Oncology

HEMATOLOGICAL ONCOLOGY, Issue 4 2003
Article first published online: 15 JAN 200
In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of hematological oncology. Each bibliography is divided into 14 sections: 1 Books, Reviews & Symposia; 2 General; Leukemias: 3 Lymphoblastic; 4 Myeloid & Myelodysplastic Syndromes; 5 Chronic; 6 Others; Lymphomas: 7 Hodgkin's; 8 Non-Hodgkin's; 9 Plasmacytomas/Multiple Myelomas; 10 Others; 11 Bone Marrow Transplantation; 12 Cytokines; 13 Diagnosis; 14 Cytogenetics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. [source]

Current Awareness in Hematological Oncology

HEMATOLOGICAL ONCOLOGY, Issue 4 2002
Article first published online: 5 DEC 200
In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of hematological oncology. Each bibliography is divided into 14 sections: 1 Books, Reviews & Symposia; 2 General; Leukemias: 3 Lymphoblastic; 4 Myeloid & Myelodysplastic Syndromes; 5 Chronic; 6 Others; Lymphomas: 7 Hodgkin's; 8 Non-Hodgkin's; 9 Plasmacytomas/Multiple Myelomas; 10 Others; 11 Bone Marrow Transplantation; 12 Cytokines; 13 Diagnosis; 14 Cytogenetics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. [source]

Current Awareness in Hematological Oncology

HEMATOLOGICAL ONCOLOGY, Issue 3 2002
Article first published online: 29 AUG 200
In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of hematological oncology. Each bibliography is divided into 14 sections: 1 Books, Reviews & Symposia; 2 General; Leukemias: 3 Lymphoblastic; 4 Myeloid & Myelodysplastic Syndromes; 5 Chronic; 6 Others; Lymphomas: 7 Hodgkin's; 8 Non-Hodgkin's; 9 Plasmacytomas/Multiple Myelomas; 10 Others; 11 Bone Marrow Transplantation; 12 Cytokines; 13 Diagnosis; 14 Cytogenetics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. [source]

Current Awareness in Hematological Oncology

HEMATOLOGICAL ONCOLOGY, Issue 4 2001
Article first published online: 17 DEC 200
In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of hematological oncology. Each bibliography is divided into 14 sections: 1 Books, Reviews & Symposia; 2 General; Leukemias: 3 Lymphoblastic; 4 Myeloid & Myelodysplastic Syndromes; 5 Chronic; 6 Others; Lymphomas: 7 Hodgkin's; 8 Non-Hodgkin's; 9 Plasmacytomas/Multiple Myelomas; 10 Others; 11 Bone Marrow Transplantation; 12 Cytokines; 13 Diagnosis; 14 Cytogenetics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. [source]

Modulation of antigen expression in B-cell precursor acute lymphoblastic leukemia during induction therapy is partly transient: Evidence for a drug-induced regulatory phenomenon.

CYTOMETRY, Issue 3 2010
Results of the AIEOP-BFM-ALL-FLOW-MRD-Study Group
Abstract Background: Changes of antigen expression on residual blast cells of acute lymphoblastic leukemia (ALL) occur during induction treatment. Many markers used for phenotyping and minimal residual disease (MRD) monitoring are affected. Glucocorticoid (GC)-induced expression modulation has been causally suspected, however, subclone selection may also cause the phenomenon. Methods: We investigated this by following the phenotypic evolution of leukemic cells with flow cytometry from diagnosis to four time points during and after GC containing chemotherapy in the 20 (of 360 consecutive) B-cell precursor patients with ALL who had persistent MRD throughout. Results: The early expression changes of CD10 and CD34 were reversible after stop of GC containing chemotherapy. Modulation of CD20 and CD45 occurred mostly during the GC phase, whereas CD11a also changed later on. Blast cells at diagnosis falling into gates designed according to "shifted" phenotypes from follow-up did not form clusters and were frequently less numerous than later on. Conclusions: Our data support the idea that drug-induced modulation rather than selection causes the phenomenon. The good message for MRD assessment is that modulation is transient in at least two (CD10 and CD34) of the five prominent antigens investigated and reverts to initial aberrant patterns after stop of GC therapy, whereas CD20 expression gains new aberrations exploitable for MRD detection. © 2010 Clinical Cytometry Society [source]

Overexpression of CD49f in precursor B-cell acute lymphoblastic leukemia: Potential usefulness in minimal residual disease detection

CYTOMETRY, Issue 2 2009
Joseph A. DiGiuseppe
Abstract Background: The persistence of minimal residual disease (MRD) following therapy is an established prognostic factor in precursor B-cell acute lymphoblastic leukemia (pB-ALL). Detection of MRD in pB-ALL by flow cytometric immunophenotyping requires demonstration of abnormal antigen expression in leukemic B-cell precursors relative to that of normal B-cell precursors. The gene encoding CD49f (integrin ,-6) is one of several whose overexpression in pB-ALL at diagnosis has been associated with the subsequent detection of MRD. However, whether CD49f might be a useful reagent in the immunophenotypic detection of MRD in pB-ALL has not been evaluated. Methods: We evaluated CD49f expression by 4-color flow cytometry in normal B-cell precursors, and in a series of cases of pB-ALL, both at diagnosis and at intervals following the initiation of therapy. Results: In 10 control marrow samples, CD49f was undetectable or extremely dim in all but a minor subset of normal CD19+ B-lineage cells, whereas in 11 of 15 cases (73%) of pB-ALL, CD49f was moderate or bright at diagnosis, and persisted or became brighter after initiation of therapy. MRD detected using CD49f corresponded precisely with that obtained using a standard panel of antibodies, and permitted the detection of leukemic populations comprising as little as 0.02% of cells. Of the four pB-ALL cases in which CD49f was undetectable or dim at diagnosis, MRD was detected in two; in one of these, CD49f expression was substantially increased in the leukemic cells that persisted following initiation of therapy. Conclusions: CD49f is commonly overexpressed in p-B-ALL, and represents a potentially useful marker for the immunophenotypic detection of MRD. © 2008 Clinical Cytometry Society How to cite this article: DiGiuseppe JA, Fuller SG, Borowitz MJ. Overexpression of CD49f in precursor B-cell acute lymphoblastic leukemia: potential usefulness in minimal residual disease detection. Cytometry Part B 2008. [source]

Prednisone induces immunophenotypic modulation of CD10 and CD34 in nonapoptotic B-cell precursor acute lymphoblastic leukemia cells,

CYTOMETRY, Issue 3 2008
Giuseppe Gaipa
Abstract Background: Immunophenotypic modulation is induced by steroids in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients during remission induction therapy. Methods: We cultured BCP-ALL blasts from diagnostic bone marrow (BM) samples (n = 20) in the presence of prednisone on stroma layer obtained from BM-derived mesenchymal cells to maintain viability. Antigen expression was assessed by multiparametric flow cytometry. Results: Leukemia samples that sustained the treatment in vitro with prednisone, showed significative reduction of CD10 and CD34 expression compared with control, and it was comparable with that observed in residual leukemic cells of the same patients in BM at day 15 of treatment. Modulated cells were viable as determined by Annexin V staining and preserved light scattering properties. Of note, the extent of antigen modulation in vitro correlated with response to prednisone in vivo. Conclusions: The prednisone-induced immunophenotypic modulation can be reproduced in vitro and this phenomenon may reflect sensitivity to chemotherapy. © 2008 Clinical Cytometry Society [source]

Positive selection for CD90 as a purging option in acute myeloid leukemia stem cell transplants,

CYTOMETRY, Issue 1 2008
Nicole Feller
Abstract Background: Several studies showed the benefit of purging of acute myeloid leukemia (AML) stem cell transplants. We reported previously that purging by positive selection of CD34+ and CD133+ cells resulted in a 3,4 log tumor cell reduction (TCR) in CD34, and/or CD133, AML, but has been shown to be potentially applicable in only about 50% of cases. Similar to CD34 and CD133, CD90 marks the hematopoietic CD34 positive stem cells capable of full hematopoietic recovery after myeloablative chemotherapy, and therefore, in the present study, we explored whether a similar purging approach is possible using CD90. Methods: CD90 expression was established by flowcytometry in diagnosis AML on the clonogenic AML CD34+ blast population by flow cytometry. Positivity was defined as >3% CD90 (CD34+) expression on blasts. For the calculation of the efficacy of TCR by positive selection, AML blasts were recognized by either prelabeling diagnosis blasts with CD45-FITC in spiking model experiments or using expression of leukemia associated marker combinations both in spiking experiments and in real transplants. Results: In 119 patients with AML and myelodysplastic syndrome, we found coexpression of CD34 and CD90 (>3%) in 42 cases (35%). In AML patients 60 years or younger, representing the patients who are eligible for transplantation, only 23% (16/69) of the patients showed CD90 expression. Positive selection for CD90 in transplants containing CD90 negative AML resulted in a 2.8,4 log TCR in the models used. Conclusions: Purging by positive selection using CD90 can potentially be applied effectively in the majority of AML patients 60 years or younger. © 2007 Clinical Cytometry Society [source]