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Acute Myeloid Leukemia Patient (acute + myeloid_leukemia_patient)
Selected AbstractsLPXN, a member of the paxillin superfamily, is fused to RUNX1 in an acute myeloid leukemia patient with a t(11;21)(q12;q22) translocationGENES, CHROMOSOMES AND CANCER, Issue 12 2009Hai-Ping Dai RUNX1 (previously AML1) is involved in multiple recurrent chromosomal rearrangements in hematological malignances. Recently, we identified a novel fusion between RUNX1 and LPXN from an acute myeloid leukemia (AML) patient with t(11;21)(q12;q22). This translocation generated four RUNX1/LPXN and one LPXN/RUNX1 chimeric transcripts. Two representative RUNX1/LPXN fusion proteins, RL and RLs, were both found to localize in the nucleus and could bring the CBFB protein into the nucleus like the wild-type RUNX1. Both fusion proteins inhibit the ability of RUNX1 to transactivate the CSF1R promoter, probably through competition for its target sequences. Unlike RL and RLs, the LPXN/RUNX1 fusion protein LR was found to localize in the cytoplasm. Thus, we believe it has little impact on the transcriptional activity of RUNX1. We also found that fusion proteins RL, RLs, LR, and wild-type LPXN could confer NIH3T3 cells with malignant transformation characteristics such as more rapid growth, the ability to form colonies in soft agar, and the ability to form solid tumors in the subcutaneous tissue of the BALB/c nude mice. Taken together, our data indicated that the RUNX1/LPXN and LPXN/RUNX1 fusion proteins may play important roles in leukemogenesis and that deregulation of cell adhesion pathways may be pathogenetically important in AML. Our study also suggests that LPXN may play an important role in carcinogenesis. © 2009 Wiley-Liss, Inc. [source] PRDX4, a member of the peroxiredoxin family, is fused to AML1 (RUNX1) in an acute myeloid leukemia patient with a t(X;21)(p22;q22)GENES, CHROMOSOMES AND CANCER, Issue 4 2004Yanming Zhang The AML1 gene (also known as RUNX1) at 21q22 codes for core binding factor (CBF) ,, which forms a heterodimer with CBF , that acts as a transcriptional activating factor. CBF is a critical regulator in the generation and differentiation of definitive hematopoietic stem cells and is frequently disrupted in leukemia through chromosome translocations. We cloned a novel AML1 partner gene, PRDX4, in an X;21 translocation in a 74-year-old male patient diagnosed with acute myeloid leukemia,M2. Chromosome analysis detected a t(X;21)(p22;q22) as the sole abnormality in bone marrow samples. The involvement of AML1 was confirmed by fluorescence in situ hybridization studies. Using 3, RACE-PCR, we cloned a fusion between exon 5 of AML1 and exon 2 of PRDX4. RT-PCR confirmed the fusion and detected another fusion between exon 6 of AML1 and exon 2 of PRDX4, indicating alternative splicing of exon 6 of AML1 in the fusion transcripts. PRDX4 is one of six peroxiredoxin-family genes that are highly conserved in eukaryotes and prokaryotes and are ubiquitously expressed. Peroxiredoxin genes exhibit thioredoxin-dependent peroxidase activity and have been implicated in a number of other cellular functions such as cell proliferation and differentiation. PRDX4 plays a regulatory role in the activation of the transcription factor NF-,B and is significantly down-regulated in acute promyelocytic leukemia. This is the first example of antioxidant enzyme involvement in a chromosome translocation in leukemia. © 2004 Wiley-Liss, Inc. [source] Complete resolution of leukemia cutis with sorafenib in an acute myeloid leukemia patient with FLT3-ITD mutation,AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2009Sung Ho Lee No abstract is available for this article. [source] Elevated AF1q expression is a poor prognostic marker for adult acute myeloid leukemia patients with normal cytogenetics,AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2009Crawford J. Strunk Nearly half of the patients with newly diagnosed acute myeloid leukemia have normal cytogenetics (NC-AML) and are classified as intermediate risk, but their 5-year overall survival (OS) ranges from 24 to 42%. Therefore, molecular biomarkers to identify poor-risk patients are needed. Elevated AF1q expression in the absence of specific poor cytogenetics is associated with poor outcomes in pediatric patients with AML and adult patients with myelodysplastic syndrome. We examined AF1q expression in 290 patients with NC-AML. We found that patients with low AF1q (n = 73) expression (AF1qlow) have better OS (P = 0.026), disease-free survival (P = 0.1), and complete remission rate (P = 0.06) when compared with patients with high AF1q expression (AF1qhighn = 217). The patients with AF1qhigh had significantly greater incidence of concurrent tyrosine kinase3 internal tandem duplication. A subgroup of the patients with AF1qhigh who received allogeneic stem cell transplantation (SCT) had a significant better relapse-free survival when compared with patients who received chemotherapy/autologous SCT (P = 0.04). This study suggests that high AF1q expression is a poor prognostic marker for adult patients with NC-AML. [source] | ||||||||||