A Synopsis Clonal Hematopoiesis of Indeterminate Potential in Hematology

Zerdan, Maroun Bou; Nasr, Lewis; Saba, Ludovic; Meouchy, Paul; Safi, Nadine; Allam, Sabine; Bhandari, Jenish; Chaulagain, Chakra P

doi:10.3390/cancers14153663

Cited by 5 publications

(1 citation statement)

References 47 publications

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“…CHIP is rarely detected in the younger population but occurs at a frequency of up to 10% in those over 70 years [273]. Frequently mutated genes in CH are the epigenetic regulators Tet Methylcytosine Dioxygenase 2 (TET2), DNA methyltransferase (DNMT3A), and additional sex combs like 1 (ASXL1) [273,274]. CHIP-associated variants are indicators of high-risk disease with poor prognosis and response to treatment in MM, particularly in those undergoing transplant [275,276].…”

Section: Clonal Hematopoiesis and Development Of Multiple Myelomamentioning

confidence: 99%

Good Cop, Bad Cop: Profiling the Immune Landscape in Multiple Myeloma

Sharma,

Choudhary

2023

Biomolecules

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Multiple myeloma (MM) is a dyscrasia of plasma cells (PCs) characterized by abnormal immunoglobulin (Ig) production. The disease remains incurable due to a multitude of mutations and structural abnormalities in MM cells, coupled with a favorable microenvironment and immune suppression that eventually contribute to the development of drug resistance. The bone marrow microenvironment (BMME) is composed of a cellular component comprising stromal cells, endothelial cells, osteoclasts, osteoblasts, and immune cells, and a non-cellular component made of the extracellular matrix (ECM) and the liquid milieu, which contains cytokines, growth factors, and chemokines. The bone marrow stromal cells (BMSCs) are involved in the adhesion of MM cells, promote the growth, proliferation, invasion, and drug resistance of MM cells, and are also crucial in angiogenesis and the formation of lytic bone lesions. Classical immunophenotyping in combination with advanced immune profiling using single-cell sequencing technologies has enabled immune cell-specific gene expression analysis in MM to further elucidate the roles of specific immune cell fractions from peripheral blood and bone marrow (BM) in myelomagenesis and progression, immune evasion and exhaustion mechanisms, and development of drug resistance and relapse. The review describes the role of BMME components in MM development and ongoing clinical trials using immunotherapeutic approaches.

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Section: Clonal Hematopoiesis and Development Of Multiple Myelomamentioning

confidence: 99%

Good Cop, Bad Cop: Profiling the Immune Landscape in Multiple Myeloma

Sharma,

Choudhary

2023

Biomolecules

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The role of clonal progression leading to the development of therapy-related myeloid neoplasms

Guarnera,

Pascale,

Hajrullaj

et al. 2024

Ann Hematol

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Therapy-related myeloid neoplasms (t-MN) are characterized by aggressive features and a dismal prognosis. Recent evidence suggests a higher incidence of t-MN in individuals harboring clonal hematopoiesis of indeterminate potential (CHIP). In order to gain insight into CHIP-driven malignant progression, we gathered data from ten published reports with available detailed patient characteristics at the time of primary malignancy and t-MN development. Detailed clinical and molecular information on primary malignancy and t-MN were available for 109 patients: 43% harbored at least one somatic mutation at the time of the primary malignancy. TET2 and TP53 mutations showed an increasing variant allele frequency from CHIP to t-MN. ASXL1-associated CHIP significantly correlated with the emergence of TET2 and CEBPA mutations at t-MN, as well as U2AF1-driven CHIP with EZH2 mutation and both IDH2 and SRSF2-driven CHIP with FLT3 mutation. DNMT3A-driven CHIP correlated with a lower incidence of TP53 mutation at t-MN. In contrast, TP53-driven CHIP correlated with a complex karyotype and a lower tendency to acquire new mutations at t-MN. Patients with multiple myeloma as their first malignancy presented a significantly higher rate of TP53 mutations at t-MN. The progression from CHIP to t-MN shows different scenarios depending on the genes involved. A deeper knowledge of CHIP progression mechanisms will allow a more reliable definition of t-MN risk.

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