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

doi:10.1038/leu.2015.67

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

College of Medicine and Public Health

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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 language	English
Pages (from-to)	2101-2104
Number of pages	4
Journal	Leukemia
Volume	29
Issue number	10
DOIs	https://doi.org/10.1038/leu.2015.67
Publication status	Published - 1 Oct 2015

Bibliographical note

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.

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

@article{a3c2426e0ad54f198371dcfd17a19e98,

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

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.",

keywords = "Acute myeloid leukemia, remission, chemotherapy, stem-cell",

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

note = "This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article{\textquoteright}s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.",

year = "2015",

month = oct,

day = "1",

doi = "10.1038/leu.2015.67",

language = "English",

volume = "29",

pages = "2101--2104",

journal = "Leukemia",

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Hahn, CN, Ross, DM, Feng, J, Beligaswatte, A, Hiwase, DK, Parker, WT, Ho, M, Zawitkowski, M, Ambler, KL, Cheetham, GD, Lee, YK, Babic, M, Butcher, CM, Engler, GA, Brown, AL, D'Andrea, RJ, Lewis, ID, Schreiber, AW, To, LB & Scott, HS 2015, 'A tale of two siblings: Two cases of AML arising from a single pre-leukemic DNMT3A mutant clone', Leukemia, vol. 29, no. 10, pp. 2101-2104. https://doi.org/10.1038/leu.2015.67

TY - JOUR

T1 - A tale of two siblings

T2 - Two cases of AML arising from a single pre-leukemic DNMT3A mutant clone

AU - Hahn, C. N.

AU - Ross, D. M.

AU - Feng, J.

AU - Beligaswatte, A.

AU - Hiwase, D. K.

AU - Parker, W. T.

AU - Ho, M.

AU - Zawitkowski, M.

AU - Ambler, K. L.

AU - Cheetham, G. D.

AU - Lee, Y. K.

AU - Babic, M.

AU - Butcher, C. M.

AU - Engler, G. A.

AU - Brown, A. L.

AU - D'Andrea, R. J.

AU - Lewis, I. D.

AU - Schreiber, A. W.

AU - To, L. B.

AU - Scott, H. S.

N1 - This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.

PY - 2015/10/1

Y1 - 2015/10/1

N2 - 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.

AB - 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.

KW - Acute myeloid leukemia

KW - remission

KW - chemotherapy

KW - stem-cell

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UR - http://purl.org/au-research/grants/NHRMC/1024215

UR - http://purl.org/au-research/grants/NHMRC/1023059

U2 - 10.1038/leu.2015.67

DO - 10.1038/leu.2015.67

M3 - Letter

C2 - 25748685

AN - SCOPUS:84943587194

SN - 0887-6924

VL - 29

SP - 2101

EP - 2104

JO - Leukemia

JF - Leukemia

IS - 10

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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