TP53 Mutated Chronic Myelomonocytic Leukemia is Associated with Complex Genetic Abnormalities and Inferior Outcome
Recommended Citation
Ghosh SB, Xu Z, Tawil T, Liu W, Gomez-Gelvez J, Schultz D, Inamdar1 K. TP53 Mutated Chronic Myelomonocytic Leukemia is Associated with Complex Genetic Abnormalities and Inferior Outcome. Lab Invest 2024; 104(3):S1406-S1407.
Document Type
Conference Proceeding
Publication Date
3-1-2024
Publication Title
Lab Invest
Abstract
Background: Advances in gene sequencing technologies have led to detailed understanding of the molecular characterization of chronic myelomonocytic leukemia (CMML). This study aims to understand the cytogenetic and gene mutational profile of CMML patients and their impact on disease outcome. Design: 70 patients diagnosed with CMML between January 2018 to June 2023 were enrolled for the study. Clinical and laboratory data including CBC, bone marrow and genetic findings were collected from electronic medical record (EMR). Statistical analysis was performed using R 4.3.1. Kaplan-Meier log rank analysis was performed to understand the impact of the genetic mutations on survival. Results: Of the 70 patients diagnosed with CMML, 44 had complete genetic and mutational data available. The M:F ratio was 2:1 (10 black, 60 white), with age ranging from 34-99 years. 17 patients had CMML-2, 53 patients had CMML-1, two patients had other associated hematolymphoid neoplasms; 32 patients had the MD-CMML and 38 MP-CMML subtypes. The most common genetic aberrations were del7 (16%), gain of chr8 (21%) and delY (9%). The most frequent gene mutations were TET2 (39%), ASXL (35%), SRSF2 (30%), RUNX1(14%), JAK2(14%), TP53 (9%). All TP53 mutated CMMLs (VAF 40-88%) were biallelic, of the MDCMML subtype, and frequently (75%) CMML-2 with prominent trilineage dysplasia and complex karyotype in 100%. TP53 was the only defining genetic aberration in 3 while 1 patient had additional mutations of TET2, DNMT3A, NRAS and SRSF2. Three patients died within 4 months of diagnosis. 5 patients with JAK2 mutations (VAF 2-23%), were of the MP-CMML subtype with variable monocytosis and grade 0/3 -2/3 reticulin fibrosis. TP53 mutation and complex karyotype had the most significant adverse impact on survival (p <0.05) (Fig1). A combination of 3 or more mutations negatively impacted the outcome, while non-TP53 gene mutations did not significantly affect survival. The associations between the most frequent gene mutations, morphology and survival outcome analyzed in 44 patients is represented in Table 1. Conclusions: Conclusion: p53 mutated Chronic Myelomonocytic Leukemia is associated with complex genetic abnormalities and inferior outcome. Single genetic mutations did not have an independent impact on survival. A combination of 3 or more mutations negatively affected the outcome.
Volume
104
Issue
3
First Page
S1406
Last Page
S1407
