Genomic trajectory in leukemogenesis of myeloproliferative neoplasms: a case report.
Genomic trajectory in leukemogenesis of myeloproliferative neoplasms: a case report.
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DOI：
10.1186/s12920-021-00986-z
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发表时间：
2021-05-22
影响因子：
2.7
通讯作者：
Sosa R
中科院分区：
文献类型：
--
作者：
Chen Y;Talukder R;Merritt BY;King KY;Kimmel M;Rivero G;Sosa R
We report a patient with Essential Thrombocythemia (ET), subsequently diagnosed with concurrent myeloid and lymphoid leukemia. Generally, the molecular mechanisms underlying leukemic transformation of Philadelphia-negative myeloproliferative neoplasms (Ph-MPN) are poorly understood. Risk of transformation to acute myelogenous leukemia (AML) is low; transformation to both AML and acute lymphoblastic leukemia (ALL) is extremely low. Genetic defects, including allele burden, order of mutation acquisition, clonal heterogeneity and epigenetic mechanisms are important contributors to disease acceleration. A 78-year-old Caucasian female originally treated for stable ET, underwent disease acceleration and transition to myeloid sarcoma and B-cell ALL. Genomic reconstruction based on targeted sequencing revealed the presence of a large del(5q) in all three malignancies and somatic driver mutations: TET2, TP53, SF3B1, and ASXL1 at high allele frequency. We propose that the combination of genetic and molecular abnormalities led to hematopoietic stem cell (HSC) injury and disease progression through sub-clone branching. We hypothesize that ancestral reconstruction of genomic data is a useful tool to uncover subclonal events leading to transformation. The use of ancestral reconstruction of genomic data sheds light on the unique clinical scenario described in this case report. By determining the mutational profile of tumors at several timepoints and deducing the most parsimonious relationship between them, we propose a reconstruction of their origin. We propose that blast progression originated from subclonal events with malignant potential, which coexisted with but did not originate from JAK2 p.V617F-positive ET. We conclude that the application of genomic reconstruction enhances our understanding of leukemogenesis by identifying the timing of molecular events, potentially leading to better chemotherapy choices as well as the development of new targeted therapies.
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影响因子：
3.5
作者：
Giagounidis, Aristoteles;Mufti, Ghulam J.;Fenaux, Pierre;Germing, Ulrich;List, Alan;MacBeth, Kyle J.
通讯作者：
MacBeth, Kyle J.
DOI：
10.1073/pnas.0610477104
发表时间：
2007-07-03
影响因子：
11.1
作者：
Pellagatti, Andrea;Jaedersten, Martin;Helistroem-Lindberg, Eva
通讯作者：
Helistroem-Lindberg, Eva
DOI：
10.1056/nejmoa1605949
发表时间：
2016-11-24
期刊：
The New England journal of medicine
影响因子：
--
作者：
Welch JS;Petti AA;Miller CA;Fronick CC;O'Laughlin M;Fulton RS;Wilson RK;Baty JD;Duncavage EJ;Tandon B;Lee YS;Wartman LD;Uy GL;Ghobadi A;Tomasson MH;Pusic I;Romee R;Fehniger TA;Stockerl-Goldstein KE;Vij R;Oh ST;Abboud CN;Cashen AF;Schroeder MA;Jacoby MA;Heath SE;Luber K;Janke MR;Hantel A;Khan N;Sukhanova MJ;Knoebel RW;Stock W;Graubert TA;Walter MJ;Westervelt P;Link DC;DiPersio JF;Ley TJ
通讯作者：
Ley TJ
影响因子：
0.7
作者：
Alhuraiji, Ahmad;Naqvi, Kiran;Bose, Prithviraj
通讯作者：
Bose, Prithviraj
影响因子：
2.6
作者：
Xie, Wei;Chen, Zhining;Tang, Guiling
通讯作者：
Tang, Guiling