Mutations in chronic myelomonocytic leukemia and their prognostic relevance

J Jian; Y Qiao; Y Li; Y Guo; H Ma; B Liu

doi:10.1007/s12094-021-02585-x

Mutations in chronic myelomonocytic leukemia and their prognostic relevance

Clin Transl Oncol. 2021 Sep;23(9):1731-1742. doi: 10.1007/s12094-021-02585-x. Epub 2021 Apr 16.

Authors

J Jian^#¹, Y Qiao^#², Y Li¹, Y Guo¹, H Ma^{3

4}, B Liu^{5

6}

Affiliations

¹ The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China.
² Institute of Hematology, Xi'an Central Hospital, Xi'an, Shaanxi, China.
³ The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China. [email protected].
⁴ Department of Hematology, The First Affiliated Hospital, Lanzhou University, 1 Donggangxilu street, Lanzhou, Gansu, China. [email protected].
⁵ The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China. [email protected].
⁶ Department of Hematology, The First Affiliated Hospital, Lanzhou University, 1 Donggangxilu street, Lanzhou, Gansu, China. [email protected].

^# Contributed equally.

PMID: 33861431
DOI: 10.1007/s12094-021-02585-x

Abstract

Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy that overlaps with myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) and tends to transform into acute myeloid leukemia (AML). Among cases of CMML, > 90% have gene mutations, primarily involving TET2 (~ 60%), ASXL1 (~ 40%), SRSF2 (~ 50%), and the RAS pathways (~ 30%). These gene mutations are associated with both the clinical phenotypes and the prognosis of CMML, special CMML variants and pre-phases of CMML. Cytogenetic abnormalities and the size of genome are also associated with prognosis. Meanwhile, cases with ASXL1, DNMT3A, NRAS, SETBP1, CBL and RUNX1 mutations may have inferior prognoses, but only ASXL1 mutations were confirmed to be independent predictors of the patient outcome and were included in three prognostic models. Novel treatment targets related to the various gene mutations are emerging. Therefore, this review provides new insights to explore the correlations among gene mutations, clinical phenotypes, prognosis, and novel drugs in CMML.

Keywords: Chronic myelomonocytic leukemia; Gene mutations; Novel drugs; Prognosis.

Publication types

Review

MeSH terms

Antineoplastic Agents / therapeutic use*
Carrier Proteins / genetics
Chromosome Aberrations
Core Binding Factor Alpha 2 Subunit / genetics
DNA Methylation
DNA Methyltransferase 3A / genetics
DNA-Binding Proteins / genetics
Dioxygenases / genetics
Epigenesis, Genetic
Epigenetic Repression
GTP Phosphohydrolases / genetics
Genes, ras
Genome Size
Humans
Leukemia, Myeloid, Acute / genetics
Leukemia, Myelomonocytic, Chronic / drug therapy*
Leukemia, Myelomonocytic, Chronic / genetics*
Leukemia, Myelomonocytic, Chronic / mortality
Membrane Proteins / genetics
Mutation*
Myelodysplastic Syndromes / genetics
Nuclear Proteins / genetics
Phenotype
Prognosis
Proto-Oncogene Proteins c-cbl / genetics
Repressor Proteins / genetics
Serine-Arginine Splicing Factors / genetics
Signal Transduction / genetics

Substances

ASXL1 protein, human
Antineoplastic Agents
Carrier Proteins
Core Binding Factor Alpha 2 Subunit
DNA-Binding Proteins
DNMT3A protein, human
Membrane Proteins
Nuclear Proteins
RUNX1 protein, human
Repressor Proteins
SETBP1 protein, human
SRSF2 protein, human
Serine-Arginine Splicing Factors
Dioxygenases
TET2 protein, human
DNA Methyltransferase 3A
Proto-Oncogene Proteins c-cbl
GTP Phosphohydrolases
NRAS protein, human
CBL protein, human