ISSN 2997-1036
International Journal of Hematology | Vol. 14, No. 8, August 2023 | pp. 57–64
DOI: 10.46882/2023/IJH/000162
Original Article
Title: Prevalence and molecular profiles of PPM1D and TP53 somatic mutations in therapy-related clonal hematopoiesis 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 peripheral blood leucocytes, 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. 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 cytopenia, next-generation sequencing
Manuscript Timeline: Received: May 10, 2023; Revised: June 15, 2023; Accepted: July 09, 2023; Published: August 16, 2023