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Your search keyword '"Drabkin, H.A."' showing total 24 results
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24 results on '"Drabkin, H.A."'

3. Homeobox gene expression in acute myeloid leukemia is linked to typical underlying molecular aberrations

Author

Kramarzova, K.S. (Karolina Skvarova), Fiser, K. (Karel), Mejstříková, E. (Ester), Rejlova, K. (Katerina), Zaliova, M. (Marketa), Fornerod, M.W.J. (Maarten), Drabkin, H.A. (Harry), Heuvel-Eibrink, M.M. (Marry) van den, Stary, J. (Jan), Trka, J. (Jan), Starkova, J. (Julia), Kramarzova, K.S. (Karolina Skvarova), Fiser, K. (Karel), Mejstříková, E. (Ester), Rejlova, K. (Katerina), Zaliova, M. (Marketa), Fornerod, M.W.J. (Maarten), Drabkin, H.A. (Harry), Heuvel-Eibrink, M.M. (Marry) van den, Stary, J. (Jan), Trka, J. (Jan), and Starkova, J. (Julia)

Abstract

__Background:__ Although distinct patterns of homeobox (HOX) gene expression have been described in defined cytogenetic and molecular subsets of patients with acute myeloid leukemia (AML), it is unknown whether these patterns are the direct result of transcriptional alterations or rather represent the differentiation stage of the leukemic cell. __Method:__ To address this question, we used qPCR to analyze mRNA expression of HOXA and HOXB genes in bone marrow (BM) samples of 46 patients with AML and sorted subpopulations of healthy BM cells. These various stages of myeloid differentiation represent matched counterparts of morphological subgroups of AML. To further study the transcriptional alterations of HOX genes in hematopoiesis, we also analyzed gene expression of epigenetic modifiers in the subpopluations of healthy BM and leukemic cells. __Results:__ Unsupervised hierarchical clustering divided the AMLs into five clusters characterized by the presence of prevalent molecular genetic aberrations. Notably, the impact of genotype on HOX gene expression was significantly more pronounced than that of the differentiation stage of the blasts. This driving role of molecular aberrations was best exemplified by the repressive effect of the PML-RARa fusion gene on HOX gene expression, regardless of the presence of the FLT3/ITD mutation. Furthermore, HOX gene expression was positively correlated with mRNA levels of histone demethylases (JMJD3 and UTX) and negatively correlated with gene expression of DNA methyltranferases. No such relationships were observed in subpopulations of healthy BM cells. __Conclusion:__ Our results demonstrate that specific molecular genetic aberrations, rather than differentiation per se, underlie the observed differences in HOX gene expression in AML. Moreover, the observed correlations between epigenetic modifiers and HOX ex pression that are specific to malignant hematopoiesis, suggest their potential causal relationships.

Published
2014
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14. Quantitative HOX expression in chromosomally defined subsets of acute myelogenous leukemia.

Author

Drabkin, H.A., Parsy, C., Ferguson, K., Guilhot, F., Lacotte, L., Roy, L., Zeng, C., Baron, A., Hunger, S.P., Varella-Garcia, M., Gemmil, R., Brizard, F., Brizard, A., and Roche, J.

Subjects
*GENE expression, *ACUTE myeloid leukemia
Abstract

We used a degenerate RT-PCR screen and subsequent realtime quantitative RT-PCR assays to examine the expression of HOX and TALE-family genes in 34 cases of chromosomally defined AML for which outcome data were available. AMLs with favorable cytogenetic features were associated with low overall HOX gene expression whereas poor prognostic cases had high levels. Characteristically, multiple HOXA family members including HOXA3-HOXA10 were jointly overexpressed in conjunction with HOXB3, HOXB6, MEIS1 and PBX3. Higher levels of expression were also observed in the FAB subtype, AMLMl. Spearmann correlation coefficients indicated that the expression levels for many of these genes were highly interrelated. While we did not detect any significant correlations between HOX expression and complete response rates or age in this limited set of patients, there was a significant correlation between event-free survival and HOXA7 with a trend toward significance for HoxA9, HoxA4 and HoxA5. While patients with elevated HOX expression did worse, there were notable exceptions. Thus, although HOX overexpression and clinical resistance to chemotherapy often coincide, they are not inextricably linked. Our results indicate that quantitative HOX analysis has the potential to add new information to the management of patients with AML, especially where characteristic chromosomal alterations are lacking. [ABSTRACT FROM AUTHOR]

Published
2002
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16. Assignment of the human heart tetrodotoxin-resistant voltage-gated Na+channel α-subunit gene (SCN5A) to band 3p21

Author

George, A.L., Varkony, T.A., Drabkin, H.A., Han, J., Knops, J.F., Finley, W.H., Brown, G.B., Ward, D.C., and Haas, M.

Abstract

The chromosomal location of SCN5A, the gene encoding the principal voltage-gated Na+ channel expressed in human heart, has been determined by three independent methodologies: somatic cell hybrid mapping, chromosomal micro-dissection-polymerase chain reaction, and fluorescence in situ hybridization. The SCN5A gene was assigned to the short arm of chromosome 3 (band 3p21) by all three approaches. These data are further evidence that striated muscle Na+ channel genes are dispersed in the genome.

Published
1995
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18. Human chromosome 21-encoded cDNA clones

Author

Neve, Rachael L, primary, Stewart, Gordon D, additional, Newcomb, Patricia, additional, Van Keuren, Margaret L, additional, Patterson, David, additional, Drabkin, H.A, additional, and Kurnit, David M, additional

Published
1986
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