TY - JOUR
T1 - The Impact of Clonal Hierarchy and Heterogeneity on Phenotypic Manifestations of Myelodysplastic Neoplasms
AU - El Hussein, Siba
AU - Loghavi, Sanam
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/11
Y1 - 2022/11
N2 - Until recently, conventional prognostication of myelodysplastic neoplasms (MDS) was performed using the revised International Prognostic Scoring System (IPSS-R), with additional adverse prognoses conferred by select mutations. Nonetheless, the clonal diversity and dynamics of coexisting mutations have been shown to alter the prognosis and treatment response in patients with MDS. Often in the process of clonal evolution, various initial hits are preferentially followed by a specific spectrum of secondary alterations, shaping the phenotypic and biologic features of MDS. Our ability to recapitulate the clonal ontology of MDS is a necessary step toward personalized therapy and the conceptualization of a better classification system, which ideally would take into consideration all genomic aberrations and their inferred clonal architecture in individual cases. In this review, we summarize our current understanding of the molecular landscape of MDS and the role of mutational combinations, clonal burden, and clonal hierarchy in defining the clinical fate of the disease.
AB - Until recently, conventional prognostication of myelodysplastic neoplasms (MDS) was performed using the revised International Prognostic Scoring System (IPSS-R), with additional adverse prognoses conferred by select mutations. Nonetheless, the clonal diversity and dynamics of coexisting mutations have been shown to alter the prognosis and treatment response in patients with MDS. Often in the process of clonal evolution, various initial hits are preferentially followed by a specific spectrum of secondary alterations, shaping the phenotypic and biologic features of MDS. Our ability to recapitulate the clonal ontology of MDS is a necessary step toward personalized therapy and the conceptualization of a better classification system, which ideally would take into consideration all genomic aberrations and their inferred clonal architecture in individual cases. In this review, we summarize our current understanding of the molecular landscape of MDS and the role of mutational combinations, clonal burden, and clonal hierarchy in defining the clinical fate of the disease.
KW - clonal heterogeneity
KW - clonal succession
KW - flow cytometry analysis
KW - MDS
KW - molecular
KW - myelodysplastic neoplasm
KW - myelodysplastic syndrome
KW - scoring system
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U2 - 10.3390/cancers14225690
DO - 10.3390/cancers14225690
M3 - Review article
C2 - 36428782
AN - SCOPUS:85142478003
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 22
M1 - 5690
ER -