Integrative genomic and transcriptomic profiling reveals distinct molecular subsets in adult mixed phenotype acute leukemia.

Autor:	Wang Q; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Cai WZ; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Wang QR; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Zhu MQ; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Yan LZ; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Yu Y; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Bao XB; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Shen HJ; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Yao H; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Xie JD; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Zhang TT; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Zhang L; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Xu XY; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Shan Z; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Liu H; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Cen JN; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Liu DD; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Pan JL; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Lu DR; Key Laboratory of Birth Defects and Reproductive Health of National Health Commission, Chongqing Population and Family Planning, Science and Technology Research Institute, Chongqing, People's Republic of China.; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, People's Republic of China., Chen J; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Xu Y; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Zhang R; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China., Wang Y; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Xue SL; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Miao M; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Han Y; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Tang XW; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Qiu HY; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Sun AN; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Huang JY; Biomedical Big Data Center, Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.; Zhejiang University Cancer Center, Zhejiang University, Hangzhou, People's Republic of China., Dai HP; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Wu DP; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China., Chen SN; National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China.
Jazyk:	angličtina
Zdroj:	American journal of hematology [Am J Hematol] 2023 Jan; Vol. 98 (1), pp. 66-78. Date of Electronic Publication: 2022 Oct 31.
DOI:	10.1002/ajh.26758
Abstrakt:	Mixed phenotype acute leukemia (MPAL) is a subtype of leukemia in which lymphoid and myeloid markers are co-expressed. Knowledge regarding the genetic features of MPAL is lacking due to its rarity and heterogeneity. Here, we applied an integrated genomic and transcriptomic approach to explore the molecular characteristics of 176 adult patients with MPAL, including 86 patients with T-lymphoid/myeloid MPAL (T/My MPAL-NOS), 42 with Ph+ MPAL, 36 with B-lymphoid/myeloid MPAL (B/My MPAL-NOS), 4 with t(v;11q23), and 8 with MPAL, NOS, rare types. Genetically, T/My MPAL-NOS was similar to B/T MPAL-NOS but differed from Ph+ MPAL and B/My MPAL-NOS. T/My MPAL-NOS exhibited higher CEBPA, DNMT3A, and NOTCH1 mutations. Ph+ MPAL demonstrated higher RUNX1 mutations. B/T MPAL-NOS showed higher NOTCH1 mutations. By integrating next-generation sequencing and RNA sequencing data of 89 MPAL patients, we defined eight molecular subgroups (G1-G8) with distinct mutational and gene expression characteristics. G1 was associated with CEBPA mutations, G2 and G3 with NOTCH1 mutations, G4 with BCL11B rearrangement and FLT3 mutations, G5 and G8 with BCR::ABL1 fusion, G6 with KMT2A rearrangement/KMT2A rearrangement-like features, and G7 with ZNF384 rearrangement/ZNF384 rearrangement-like characteristics. Subsequently, we analyzed single-cell RNA sequencing data from five patients. Groups G1, G2, G3, and G4 exhibited overexpression of hematopoietic stem cell disease-like and common myeloid progenitor disease-like signatures, G5 and G6 had high expression of granulocyte-monocyte progenitor disease-like and monocyte disease-like signatures, and G7 and G8 had common lymphoid progenitor disease-like signatures. Collectively, our findings indicate that integrative genomic and transcriptomic profiling may facilitate more precise diagnosis and develop better treatment options for MPAL. (© 2022 Wiley Periodicals LLC.)
Databáze:	MEDLINE
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