Research Progress in Clonal Evolution of Classical Myeloproliferative Neoplasms
WANG Di, ZHAO Yanhong, LIANG Yipeng, TONG Jingyuan*, SHI Lihong*
Classical Philadelphia chromosome-negative MPNs (myeloproliferative neoplasms) are a group of hematopoietic stem cell-derived clonal disorders characterized by abnormal proliferation of some or all myeloid lineages often with increased cells in the peripheral blood. Most of the patients carry detectable somatic driver mutations, and MPN-related gene mutations contain driver mutations in JAK2, CALR and MPL and passenger mutations such as TET2 and DNMT3A, etc. Subsequently, undergoing a period of complex clonal evolution, MPNs could evolve from a chronic phase to an accelerated phase, and ultimately a terminal blast phase, which typically presents as an AML (acute myeloid leukemia) with more complicated structure of mutant clones. These somatic mutations and consequent CH (clonal hematopoiesis) are likely to play a crucial part in the occurrence and development of MPNs. In consequence, probing into the selective pressures that contribute to initiating CH will provide greater insights into the molecular mechanisms of formation and evolution of MPNs. In view of these aspects, selective pressures that derive from aging, therapy, microenvironmental alterations and stochastic process, and MPN-related gene mutations will be summarized in this review.
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