Morphologic, immunophenotypic, and molecular genetic comparison study in patients with clonal cytopenia of undetermined significance, myelodysplastic syndrome, and acute myeloid leukemia with myelodysplasia-related changes: A single institution experience.

Autor: Gao L; Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA., Hyter S; Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA., Zhang D; Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA., Kelting S; Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA., Woodroof J; Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA., Abdallah AO; Division of Hematologic Malignancies & Cellular Therapeutics, Department of Internal Medicine, University of Kansas Medical Center, Westwood, Kansas, USA., Yacoub A; Division of Hematologic Malignancies & Cellular Therapeutics, Department of Internal Medicine, University of Kansas Medical Center, Westwood, Kansas, USA., McGuirk J; Division of Hematologic Malignancies & Cellular Therapeutics, Department of Internal Medicine, University of Kansas Medical Center, Westwood, Kansas, USA., Abdelhakim H; Division of Hematologic Malignancies & Cellular Therapeutics, Department of Internal Medicine, University of Kansas Medical Center, Westwood, Kansas, USA., Godwin AK; Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA., Cui W; Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
Jazyk: angličtina
Zdroj: International journal of laboratory hematology [Int J Lab Hematol] 2022 Aug; Vol. 44 (4), pp. 738-749. Date of Electronic Publication: 2022 Mar 29.
DOI: 10.1111/ijlh.13840
Abstrakt: Introduction: Next-generation sequencing (NGS) analysis showed clonal cytopenia of undetermined significance (CCUS) as an immediate precursor to myelodysplastic syndrome (MDS).
Methods: We evaluated and compared morphologic, multiparametric flow cytometry (MFC), and molecular genetic findings in patients with CCUS (n = 37), MDS (n = 75), and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC, n = 24).
Results: CCUS patients showed variable MFC abnormalities including >2% CD34+ myeloblasts (5.8%), altered antigen expression on myeloblasts, monocytes, and granulocytes (1.2, 1.5, and 0.2/case), abnormal maturation of myeloblasts (45.8%), decreased hematogones (17.6%), and decreased side scatter (SSC) of granulocytes (11.4%). CCUS patients with high-risk mutations showed significantly more MFC abnormalities. However, CCUS patients with >20% variant allelic fraction (VAF) did not show more MFC aberrations than the rest of the group. MDS patients showed significantly more MFC abnormalities compared with CCUS patients (p = 7.8E-05-0.047). Low-grade MDS patients showed significantly fewer MFC abnormalities compared with high-grade MDS or AML-MRC patients (p = 1.89E-05-0.04). AML-MRC patients showed significantly elevated blast counts, more antigen aberrations, decreased hematogones, and decreased SSC of granulocytes compared with CCUS patients (p = 2.0E-05-0.01). CCUS patients carried predominantly TET2/DNMT3A/ASXL1 mutations. They harbored fewer mutations in gene coding splicing factors compared with MDS patients (p = .0001-.02) and fewer mutations in tumor suppressor and transcription factor genes compared with AML-MRC patients (p = .0006-.02).
Conclusions: CCUS is an immediate precursor to low-grade MDS. The progression from CCUS to MDS to AML-MRC is a stepwise process that requires acquisition of mutations in splicing, transcription factor, and tumor suppressor genes with accumulations of additional MFC abnormalities.
(© 2022 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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