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MLL Rearrangement (mll + rearrangement)

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Medical Sciences	100%

Selected Abstracts

MLL/SEPTIN6 chimeric transcript from inv ins(X;11)(q24;q23q13) in acute monocytic leukemia: Report of a case and review of the literature

GENES, CHROMOSOMES AND CANCER, Issue 1 2003
Hee-Jin Kim
Rearrangements of the MLL gene on chromosome 11, band q23, are one of the most common genetic changes in acute leukemia. Reciprocal translocation is the most common form of MLL rearrangement, and the partner genes in MLL translocation are notably diverse. Involvement of the SEPTIN6 gene on Xq24 in MLL rearrangements occurs very rarely, with only six cases having been documented in the literature. Of note, the MLL/SEPTIN6 rearrangements in these cases were cryptic or complex, and it was shown that the 5,- MLL/SEPTIN6 -3, transcript resides on the derivative X chromosome rather than on the derivative chromosome 11 as in the majority of cases of MLL translocations. These observations suggested that MLL and SEPTIN6 reside on their respective chromosome loci in reverse orientation, that is, centromere-to-telomere and telomere-to-centromere, respectively. We here report a case of acute monocytic leukemia with inv ins(X;11)(q24;q23q13) in a 29-month-old child. Fluorescence in situ hybridization study revealed the break-apart 5,- MLL segment to be translocated to the derivative X chromosome, and reverse transcriptase,polymerase chain reaction followed by sequencing analysis confirmed the 5,- MLL/SEPTIN6 -3, chimeric transcript. This case is the first to provide direct cytogenetic evidence for the salient nature of the MLL/SEPTIN6 rearrangement. We reviewed clinical and cytogenetic features of all cases of 11q23 and Xq22,24 rearrangements reported up to now, including six cases where the involvement of the SEPTIN6 gene was confirmed by molecular techniques. © 2003 Wiley-Liss, Inc. [source]

LAF4, an AF4 -related gene, is fused to MLL in infant acute lymphoblastic leukemia

GENES, CHROMOSOMES AND CANCER, Issue 1 2002
Anne R.M. von Bergh
Infant acute lymphoblastic leukemia (ALL) with MLL gene rearrangements is characterized by a proB phenotype and a poor clinical outcome. We analyzed an infant proB ALL with t(2;11)(p15;p14) and an MLL rearrangement on Southern blot analysis. Rapid amplification of cDNA ends,polymerase chain reaction (PCR) and reverse transcriptase-PCR identified the LAF4 gene mapped on chromosome region 2q11.2,q12 as a fusion partner of the MLL gene. The LAF4 gene was identified previously by its high sequence homology to the AF4 protein and encodes a protein of 1,227 amino acids. The t(4;11)(q21;q23), creating the MLL - AF4 chimeric transcripts, is the predominant 11q23 chromosome translocation in infant ALL and is associated with an extremely poor prognosis. Our findings further suggest that fusion of MLL to one of the AF4 family members (AF4/LAF4/AF5Q31) might determine a proB-cell phenotype in infant leukemia. © 2002 Wiley-Liss, Inc. [source]

t(10;11)-Acute leukemias with MLL-AF10 and MLL-ABI1 chimeric transcripts: Specific expression patterns of ABI1 gene in leukemia and solid tumor cell lines

GENES, CHROMOSOMES AND CANCER, Issue 1 2001
Noriko Shibuya
The recurrent translocation t(10;11) is associated with acute myeloid leukemia (AML). The AF10 gene on chromosome 10 at band p12 and MLL at 11q23 fuse in the t(10;11)(p12;q23). Recently, we have identified ABI1 as a new partner gene for MLL in an AML patient with a t(10;11)(p11.2;q23). The ABI1 is a human homologue of the mouse Abl -interactor 1 (Abi1), encoding an Abl-binding protein. The ABI1 protein exhibits sequence similarity to homeotic genes, and contains several polyproline stretches and a src homology 3 (SH3) domain. To clarify the clinical features of t(10;11)-leukemias, we investigated 6 samples from acute leukemia patients with t(10;11) and MLL rearrangement and detected MLL-AF10 chimeric transcripts in 5 samples and MLL-ABI1 in one. The patient with MLL-ABI1 chimeric transcript is the second case described, thus confirming that the fusion of the MLL and ABI1 genes is a recurring abnormality. Both of the patients with MLL-ABI1 chimeric transcript are surviving, suggesting that these patients have a better prognosis than the patients with MLL-AF10. To investigate the roles of AF10 and ABI1 further, we examined the expression of these genes in various cell lines and fresh tumor samples using the reverse transcriptase-polymerase chain reaction method. Although AF10 was expressed in almost all cell lines similarly, the expression patterns of ABI1 were different between leukemia and solid tumor cell lines, suggesting the distinctive role of each isoform of ABI1 in these cell lines. We also determined the complete mouse Abi1 sequence and found that the sequence matched with human ABI1 better than the originally reported Abi1 sequence. Further functional analysis of the MLL-AF10 and MLL-ABI1 fusion proteins will provide new insights into the leukemogenesis of t(10;11)-AML. © 2001 Wiley-Liss, Inc. [source]

Etoposide-treatment and MLL rearrangements

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2008
Rolf Marschalek
No abstract is available for this article. [source]

MLL/SEPTIN6 chimeric transcript from inv ins(X;11)(q24;q23q13) in acute monocytic leukemia: Report of a case and review of the literature

Therapy-related acute lymphoblastic leukaemia with MLL rearrangements following DNA topoisomerase II inhibitors, an increasing problem: report on two new cases and review of the literature since 1992

BRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2001
Mette Klarskov Andersen
A highly increased risk of myelodysplasia (MDS) and acute myeloid leukaemia (AML) is well established in patients previously treated for other malignancies with alkylating agents or topoisomerase II inhibitors. More recently, single cases of acute lymphoblastic leukaemia (ALL), often presenting balanced translocations involving chromosome band 11q23, have been observed. We present two such cases with t(4;11)(q21;q23), one of whom had previously received only single-agent chemotherapy with 4-epi-doxorubicin. A review of the literature since 1992 including these two patients reveals a total of 23 cases of ALL or lymphoblastic lymphoma after chemotherapy presenting balanced translocations to 11q23. All 23 patients had previously received at least one topoisomerase II inhibitor, and in two patients 4-epi-doxorubicin had been administered as single-agent chemotherapy for breast cancer. The latency period to development of t-ALL was 24 months or less in 20 out of 22 cases. The MLL gene was found to be rearranged in 14 out of 14 cases, and in three out of six cases the breakpoint was at the telomeric part of the gene, as observed in most cases of AML following therapy with topoisomerase II inhibitors. These results indicate that patients with ALL and balanced translocations to chromosome band 11q23 following chemotherapy with topoisomerase II inhibitors in the future should be included with cases of MDS or AML in calculations of risk of leukaemia. [source]