Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jan 11;22(2):659.
doi: 10.3390/ijms22020659.

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

Yammy Yung  1 , Emily Lee  1 , Hiu-Tung Chu  1 , Pui-Kwan Yip  1 , Harinder Gill  1
Affiliations
Review

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

Yammy Yung et al. Int J Mol Sci. .

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Interplay between cell-intrinsic and cell-extrinsic activities in the disease initiation of MPN. MPN: myeloproliferative neoplasm; MF: myelofibrosis.
Figure 2
Figure 2
Disease initiation and progression in Ph-negative MPNs. (A) shows the acquisition of somatic driver mutations (JAK2V617F, CALR, MPL) in a haematopoietic stem cell (HSC), leading to myeloproliferation. (B) shows the acquisition of somatic driver mutation, JAK2V617F, in HSC without progression to MPN. One of the reasons is the insufficient JAK2V617F allele burden to give rise to a MPN phenotype. (C) shows the acquisition of non-driver mutations without progression to MPN, indicating the presence of clonal hematopoiesis of indeterminate potential (CHIP). (D) The presence of CHIP increases the chance of HSC to acquire driver mutations, leading to myeloproliferation. (D,E) Acquisition of additional non-driver mutations in MPN stem cells could lead to disease progression or leukemic transformation to secondary acute myeloid leukemia (sAML).
See this image and copyright information in PMC

References

    1. Tefferi A. Myeloproliferative neoplasms: A decade of discoveries and treatment advances. Am. J. Hematol. 2016;91:50–58. doi: 10.1002/ajh.24221. - DOI - PubMed
    1. Shallis R.M., Wang R., Davidoff A., Ma X., Podoltsev N.A., Zeidan A.M. Epidemiology of the classical myeloproliferative neoplasms: The four corners of an expansive and complex map. Blood Rev. 2020;42:100706. doi: 10.1016/j.blre.2020.100706. - DOI - PubMed
    1. Hultcrantz M., Ravn Landtblom A., Andréasson B., Samuelsson J., Dickman P.W., Kristinsson S.Y., Björkholm M., Andersson T.M. Incidence of myeloproliferative neoplasms—Trends by subgroup and age in a population-based study in Sweden. J. Intern. Med. 2020;287:448–454. doi: 10.1111/joim.13019. - DOI - PMC - PubMed
    1. Pellicano F., Park L., Hopcroft L.E.M., Shah M.M., Jackson L., Scott M.T., Clarke C.J., Sinclair A., Abraham S.A., Hair A., et al. hsa-mir183/EGR1-mediated regulation of E2F1 is required for CML stem/progenitor cell survival. Blood. 2018;131:1532–1544. doi: 10.1182/blood-2017-05-783845. - DOI - PMC - PubMed
    1. Kvasnicka H.M. The differential diagnosis of classical myeloproliferative neoplasms (MPN): The updated WHO criteria. Rinsho Ketsueki. 2019;60:1166–1175. - PubMed

MeSH terms