A tale of two siblings: Two cases of AML arising from a single pre-leukemic DNMT3A mutant clone

C. N. Hahn, D. M. Ross, J. Feng, A. Beligaswatte, D. K. Hiwase, W. T. Parker, M. Ho, M. Zawitkowski, K. L. Ambler, G. D. Cheetham, Y. K. Lee, M. Babic, C. M. Butcher, G. A. Engler, A. L. Brown, R. J. D'Andrea, I. D. Lewis, A. W. Schreiber, L. B. To, H. S. Scott

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Abstract

Acute myeloid leukemia (AML) patients with DNA methyltransferase 3A (DNMT3A) mutations in remission after induction chemotherapy may have hematopoiesis arising from a putative pre-leukemic clone lacking the full spectrum of mutations seen at AML diagnosis. DNMT3A mutations in hematopoietic stem cells lead to increased self-renewal capacity and dominance of the stem-cell compartment. The common DNMT3AR882H mutation is usually heterozygous and results in loss-of-function with a dominant-negative effect. DNMT3A mutations are thought to occur early in AML ontogeny, and are found in around 20% of de novo AML and in a higher proportion of secondary AML cases. In population studies clonal mutations of DNMT3A6 and other epigenetic regulators are more common with increasing age, and may contribute to a proportion of cases of age-related skewing of X-chromosome inactivation.
Original languageEnglish
Pages (from-to)2101-2104
Number of pages4
JournalLeukemia
Volume29
Issue number10
DOIs
Publication statusPublished - 1 Oct 2015

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Keywords

  • Acute myeloid leukemia
  • remission
  • chemotherapy
  • stem-cell

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    Hahn, C. N., Ross, D. M., Feng, J., Beligaswatte, A., Hiwase, D. K., Parker, W. T., Ho, M., Zawitkowski, M., Ambler, K. L., Cheetham, G. D., Lee, Y. K., Babic, M., Butcher, C. M., Engler, G. A., Brown, A. L., D'Andrea, R. J., Lewis, I. D., Schreiber, A. W., To, L. B., & Scott, H. S. (2015). A tale of two siblings: Two cases of AML arising from a single pre-leukemic DNMT3A mutant clone. Leukemia, 29(10), 2101-2104. https://doi.org/10.1038/leu.2015.67