ISSN 2997-1036
International Journal of Hematology | Vol. 15, No. 6, June 2024 | pp. 41–48
DOI: 10.46882/2024/IJH/000172
Original Article
Title: Prevalence and molecular profiles of PPM1D and TP53 somatic mutations in therapy-related myelodysplastic syndrome variants
Names of Authors: G. M. Babalola¹, I. N. Nwosu², K. S. Abubakar³
Authors’ Affiliations: ¹Department of Haematology and Blood Transfusion, Lagos University Teaching Hospital, Lagos, Nigeria; ²Department of Medicine, University of Nigeria, Nsukka, Nigeria; ³Department of Pathology, Bayero University, Kano, Nigeria
Abstract: Genotoxic stress from prior cytotoxic regimens selects for chemoresistant stem cell clones harboring specific mutations, expanding the risk of therapy-related myeloid neoplasms. This cross-sectional study investigated the mutational prevalence and clinical phenotypes of protein phosphatase Mn2+/Mg2+ dependent 1D (PPM1D) and tumor suppressor TP53 gene variations in 64 adult lymphoma survivors presenting with persistent, unexplained cytopenias post-chemotherapy. Genomic DNA was isolated from bone marrow aspirates, followed by deep next-generation sequencing assays. PPM1D exon 6 mutations were detected in 14.1% (9 of 64) of the cytopenic survivors, while TP53 variations occurred in 10.9% (7 of 64). Overlapping mutations in both DNA-damage response genes were documented in 3.1% of cases. Clinical phenotype models revealed that sub-clones with PPM1D variants exhibited extreme survival advantages under cisplatin or etoposide exposure, correlating with prolonged neutropenia and progressive marrow dysplasia consistent with therapy-related myelodysplastic syndrome. Screening for these chemoresistant variants provides essential molecular tracking vectors, helping pathologists separate benign marrow suppression from emerging pre-leukemic clonal shifts.
Keywords: Clonal hematopoiesis, PPM1D mutation, TP53 mutation, therapy-related myelodysplastic syndrome, next-generation sequencing
Manuscript Timeline: Received: March 20, 2024; Revised: April 25, 2024; Accepted: May 12, 2024; Published: June 18, 2024