Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The International Workshop on the relationship between prior therapy and balanced chromosome aberrations in therapy-related myelodysplastic syndromes (t-MDS) and therapy-related acute leukemia (t-AL) identified 79 of 511 (15.5%) patients with balanced 21q22 translocations. Patients were treated for their primary disease, including solid tumors (56%), hematologic malignancy (43%), and juvenile rheumatoid arthritis (single case), by radiation therapy (5 patients), chemotherapy (36 patients), or combined-modality therapy (38 patients). 21q translocations involved common partner chromosomes in 81% of cases: t(8;21) (n = 44; 56%), t(3;21) (n = 16; 20%), and t(16;21) (n = 4; 5%). Translocations involving 15 other partner chromosomes were also documented with involvement of AML1(CBFA2/RUNX1), identifying a total of 23 different 21q22/AML1 translocations. The data analysis was carried out on the basis of five subsets of 21q22 cases, that is, t(8;21) with and without additional aberrations, t(3;21), t(16;21), and other 21q22 translocations. Dysplastic features were present in all 21q22 cases. Therapy-related acute myeloid leukemia (t-AML) at presentation was highest in t(8;21) (82%) and lowest in t(3;21) (37.5%) patients. Cumulative drug dose exposure scores for alkylating agents (AAs) and topoisomerase II inhibitors indicated that t(3;21) patients received the most intensive therapy among the five 21q22 subsets, and the median AA score for patients with secondary chromosome 7 aberrations was double the AA score for the entire 21q22 group. All five patients who received only radiation therapy had t(8;21) t-AML. The median latency and overall survival (OS) for 21q22 patients were 39 and 14 months (mo), compared to 26 and 8 mo for 11q23 patients, 22 and 28 mo for inv(16), 69 and 7 mo for Rare recurring aberrations, and 59 and 7 mo for Unique (nonrecurring) balanced aberration (latency P < or = 0.016 for all pairwise comparisons; OS, P < or = 0.018 for all pairwise comparisons). The percentages of 21q22 patients surviving 1 year, 2 years, and 5 years were 58%, 33%, and 18%, respectively. Noticeable differences were observed in median OS between 21q22 patients (n = 7) receiving transplant (BMT) (31 mo) compared to 21q22 patients who received intensive non-BMT therapy (n = 46) (17 mo); however, this was nonsignificant because of the small sample size (log-rank, P = 0.33). t-MDS/t-AML with balanced 21q22 aberrations was associated with prior exposure to radiation, epipodophyllotoxins, and anthracyclines, dysplastic morphologic features, multiple partner chromosomes, and longer latency periods when compared to 11q23 and inv(16) t-MDS/AML Workshop subgroups. In general, patients could be divided into two prognostic risk groups, those with t(8;21) (median OS, 19 mo) and those without t(8;21) (median OS, 7 mo) leukemia (log-rank, P = 0.0007).
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PMID:21q22 balanced chromosome aberrations in therapy-related hematopoietic disorders: report from an international workshop. 1192 Dec 72

The hypomethylating agent azacitidine (AZA) is used to treat higher-risk myelodysplastic syndromes (HR-MDS) and elderly patients with low-blast count acute myeloid leukemia (LBC-AML). Platelet recovery is an early predictor of AZA response. We prospectively studied the expression profile of transcription factors, critical for late megakaryopoiesis and changes in their expression after AZA treatment in patients with HR-MDS and LBC-AML enrolled in the BMT-AZA trial (EudraCT number 2010-019673-15). Twenty-five additional patients with low-risk (LR)-MDS were also studied. At the time of diagnosis, GATA2 mRNA levels were significantly higher in MDS as compared to controls, with increasing levels from LR- to HR-MDS/AML. RUNX1 expression was also significantly higher in MDS, as compared to controls, but no differences were found between LR- and HR-MDS. Looking at biomarkers of response, we found that patients AZA responsive had higher basal GATA1 and lower FLI1 expression, compared to those with stable or progressive disease after treatment. Univariate analysis showed that increased GATA2 mRNA expression was associated with a worse overall survival. Our findings suggest that high GATA2 expression is a poor prognostic marker for survival in patients with HR-MDS and LBC-AML treated with azacitidine. Moreover, GATA1 and FLI1 mRNA expression may predict response to AZA treatment.
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PMID:Transcription factors implicated in late megakaryopoiesis as markers of outcome after azacitidine and allogeneic stem cell transplantation in myelodysplastic syndrome. 3138 32