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01-08-2018 | Case Report

Clonal dynamics in a case of acute monoblastic leukemia that later developed myeloproliferative neoplasm

Authors: Shinya Sato, Hidehiro Itonaga, Masataka Taguchi, Yasushi Sawayama, Daisuke Imanishi, Hideki Tsushima, Tomoko Hata, Yukiyoshi Moriuchi, Hiroyuki Mishima, Akira Kinoshita, Koh-ichiro Yoshiura, Yasushi Miyazaki

Published in: International Journal of Hematology | Issue 2/2018

Abstract

In acute myeloid leukemia (AML), patients may harbor pre-leukemic hematopoietic stem cells (HSCs) containing some, but not all, of the mutations observed in the leukemic cells. These pre-leukemic HSCs may survive induction chemotherapy and contribute to AML relapse by obtaining additional mutations. We report here an acute monoblastic leukemia (AMoL) patient who later developed an unclassifiable myeloproliferative neoplasm (MPN-U). Whole-exome sequencing and cluster analysis demonstrated the presence of three distinct major clones during the clinical course: (1) an AMoL clone with ASXL1, CBL, and NPM1 somatic mutations, likely associated with the pathogenesis, and GATA2, SRSF2, and TET2 mutations, (2) an AMoL remission clone, with mutated GATA2, SRSF2, and TET2 only (possibly the founding clone (pre-leukemic HSC) that survived chemotherapy), (3) a small subclone which had JAK2 mutation during the AMoL remission, appearing at MPN-U manifestation with additional mutations. These findings suggest that pre-leukemic HSCs in AML patients may give rise to non-AML myeloid malignancies. This is the first report to analyze the clonal evolution from AMoL to MPN-U, which may provide new insight into the development of myeloid malignancies.

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Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC, Welch JS, et al. Clonal evolution in relapsed acute myeloid leukemia revealed by whole-genome sequencing. Nature. 2012;481(7382):506–10.CrossRefPubMedPubMedCentral

Corces-Zimmerman MR, Hong WJ, Weissman IL, Medeiros BC, Majeti R. Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission. Proc Natl Acad Sci USA. 2014;111(7):2548–53.CrossRefPubMed

Shlush LI, Zandi S, Mitchell A, Chen WC, Brandwein JM, Gupta V, et al. Identification of pre-leukaemic haematopoietic stem cells in acute leukemia. Nature. 2014;506(7488):328–33.CrossRefPubMedPubMedCentral

Lundberg P, Karow A, Nienhold R, Looser R, Hao-Shen H, Nissen I, et al. Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. Blood. 2014;123(14):2220–8.CrossRefPubMed

Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379–90.CrossRefPubMed

Nangalia J, Massie CE, Baxter EJ, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369(25):2391–405.CrossRefPubMedPubMedCentral

Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Massé A, et al. Mutation in TET2 in myeloid cancers. N Engl J Med. 2009;360(22):2289–301.CrossRefPubMed

Miller CA, White BS, Dees ND, Griffith M, Welch JS, Griffith OL, et al. SciClone: inferring clonal architecture and tracking the spatial and temporal patterns of tumor evolution. PLoS Comput Biol. 2014;10(8):e1003665.CrossRefPubMedPubMedCentral

Malikic S, McPherson AW, Donmez N, Sahinalp CS. Clonality inference in multiple tumor samples using phylogeny. Bioinformatics. 2015;31(9):1349–56.CrossRefPubMed

10.

Stratton MR, Campbell PJ, Futreal PA. The cancer genome. Nature. 2009;458(7239):719–24.CrossRefPubMedPubMedCentral

11.

Greaves M, Maley CC. Clonal evolution in cancer. Nature. 2012;481(7381):306–13.CrossRefPubMedPubMedCentral

12.

Falini B, Martelli MP, Bolli N, Sportoletti P, Liso A, Tiacci E, et al. Acute myeloid leukemia with mutated nucleophosmin (NPM1): is it a distinct entity? Blood. 2011;117(4):1109–20.CrossRefPubMed

13.

Sportoletti P, Varasano E, Rossi R, Mupo A, Tiacci E, Vassiliou G, et al. Mouse models of NPM1-mutated acute myeloid leukemia: biological and clinical implications. Leukemia. 2015;29(2):269–78.CrossRefPubMed

14.

Steensma DP, Bejar R, Jaiswal S, Lindsley RC, Sekeres MA, Hasserjian RP, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126(1):9–16.CrossRefPubMedPubMedCentral

15.

Kunimoto H, Nakajima H. Epigenetic dysregulation of hematopoietic stem cells and preleukemic state. Int J Hematol. 2017;016(1):34–44.CrossRef

16.

Abdel-Wahab O, Adli M, LaFave LM, Gao J, Hricik T, Shih AH, et al. ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression. Cancer Cell. 2012;22(2):180–93.CrossRefPubMedPubMedCentral

17.

Kohlmann A, Grossmann V, Klein HU, Schindela S, Weiss T, Kazak B, et al. Next-generation sequencing technology reveals a characteristic pattern of molecular mutations in 72.8% of chronic myelomonocytic leukemia by detecting frequent alterations in TET2, CBL, RAS, and RUNX1. J Clin Oncol. 2010;28(24):3858–65.CrossRefPubMed

18.

Suzuki T, Kiyoi H, Ozeki K, Tomita A, Yamaji S, Suzuki R, et al. Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia. Blood. 2005;106(8):2854–61.CrossRefPubMed

19.

Greif PA, Dufour A, Konstandin NP, Ksienzyk B, Zellmeier E, Tizazu B, et al. GATA2 zinc finger 1 mutations associated with biallelic CEBPA mutations define a unique genetic entity of acute myeloid leukemia. Blood. 2012;120(2):395–403.CrossRefPubMed

20.

Hahn CN, Chong CE, Camichael CL, Wilkins EJ, Brautigan PJ, Li XC, et al. Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia. Nat Genet. 2011;43(10):1012–7.CrossRefPubMedPubMedCentral

21.

Makishima H, Yoshizato T, Yoshida K, Sekeres MA, Radivoyevitch T, Suzuki H, et al. Dynamics of clonal evolution in myelodysplastic syndromes. Nat Genet. 2017;49(2):204–12.CrossRefPubMed

22.

Prick J, de Haan G, Green AR, Kent DG. Clonal heterogeneity as a driver of disease variability in the evolution of myeloproliferative neoplasms. Exp Hematol. 2014;42(10):841–51.CrossRefPubMed

23.

Campbell PJ, Baxter EJ, Beer PA, Scott LM, Bench AJ, Huntly BJ, et al. Mutation of JAK2 in the myeloproliferative disorders: timing, clonality studies, cytogenetic associations, and role in leukemic transformation. Blood. 2006;108(10):3548–55.CrossRefPubMed

Title: Clonal dynamics in a case of acute monoblastic leukemia that later developed myeloproliferative neoplasm
Authors: Shinya Sato
Hidehiro Itonaga
Masataka Taguchi
Yasushi Sawayama
Daisuke Imanishi
Hideki Tsushima
Tomoko Hata
Yukiyoshi Moriuchi
Hiroyuki Mishima
Akira Kinoshita
Koh-ichiro Yoshiura
Yasushi Miyazaki
Publication date: 01-08-2018
Publisher: Springer Japan
Published in: International Journal of Hematology / Issue 2/2018
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-018-2419-1

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