ISSN 2997-1036
International Journal of Hematology | Vol. 17, No. 2, February 2026 | pp. 9–16
DOI: 10.46882/2026/IJH/000192
Original Article
Title: Prevalence and molecular profiles of PPM1D and TP53 somatic mutations in therapy-related acute lymphoblastic leukemia 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 lymphoid malignancies. 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 therapy-related acute lymphoblastic leukemia. 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 leukemic cohorts, 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 alkylating agent exposure, correlating with complex karyotypes and primary resistance to standard induction regimens. Screening for these chemoresistant variants provides essential molecular tracking vectors, helping pathologists separate therapy-induced acute transitions from de novo lymphoid expansions.
Keywords: Clonal hematopoiesis, PPM1D mutation, TP53 mutation, therapy-related lymphoblastic leukemia, next-generation sequencing
Manuscript Timeline: Received: November 05, 2025; Revised: December 14, 2025; Accepted: January 10, 2026; Published: February 18, 2026