Targeting Abnormal Hematopoietic Stem Cells in Chronic Myeloid Leukemia and Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms

Yammy Yung; Emily Lee; Hiu-Tung Chu; Pui-Kwan Yip; Harinder Gill

doi:10.3390/ijms22020659

Targeting Abnormal Hematopoietic Stem Cells in Chronic Myeloid Leukemia and Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms

Int J Mol Sci. 2021 Jan 11;22(2):659. doi: 10.3390/ijms22020659.

Authors

Yammy Yung¹, Emily Lee¹, Hiu-Tung Chu¹, Pui-Kwan Yip¹, Harinder Gill¹

Affiliation

¹ Division of Haematology, Medical Oncology and Haemopoietic Stem Cell transplantation, Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Abstract

Myeloproliferative neoplasms (MPNs) are unique hematopoietic stem cell disorders sharing mutations that constitutively activate the signal-transduction pathways involved in haematopoiesis. They are characterized by stem cell-derived clonal myeloproliferation. The key MPNs comprise chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). CML is defined by the presence of the Philadelphia (Ph) chromosome and BCR-ABL1 fusion gene. Despite effective cytoreductive agents and targeted therapy, complete CML/MPN stem cell eradication is rarely achieved. In this review article, we discuss the novel agents and combination therapy that can potentially abnormal hematopoietic stem cells in CML and MPNs and the CML/MPN stem cell-sustaining bone marrow microenvironment.

Keywords: chronic myeloid leukemia; myeloproliferative neoplasm; stem cells; targeted therapy.

Publication types

Review

MeSH terms

Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Autophagy
Biomarkers, Tumor
Cell Survival / drug effects
Cell Transformation, Neoplastic / genetics
Combined Modality Therapy
Disease Susceptibility*
Genetic Predisposition to Disease
Hematopoietic Stem Cells / drug effects
Hematopoietic Stem Cells / metabolism*
Hematopoietic Stem Cells / pathology
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / etiology*
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
Molecular Targeted Therapy
Myeloproliferative Disorders / etiology*
Myeloproliferative Disorders / pathology
Myeloproliferative Disorders / therapy*
Neoplastic Stem Cells / drug effects
Neoplastic Stem Cells / metabolism*
Neoplastic Stem Cells / pathology
Philadelphia Chromosome
Signal Transduction / drug effects
Stem Cell Niche
Tumor Microenvironment

Substances

Antineoplastic Agents
Biomarkers, Tumor