A Case of ABL With Biallelic TP53 Inactivation

Document Type

Conference Proceeding

Publication Date

11-2025

Publication Title

American Journal of Clinical Pathology

Abstract

Introduction/Objective: Acute myeloid leukemia (AML) is a neoplasm of the myeloid cell line characterized by proliferation of blasts in the bone marrow and peripheral blood. Clonal expansion in the bone marrow leads to decreased production of red blood cells and platelets. AML is diagnosed when >20% blasts are observed in the peripheral blood, as measured by flow cytometry. There are several risk factors associated with AML - most prominent being radiation, chemotherapy, and a variety of myeloproliferative neoplasms (MPN). Basophils are granulocytes, derived from myeloid stem cells, that circulate through the blood. Their granules contain substances such as histamine, heparin, leukotrienes, and prostaglandins which contribute to processes such as vasodilation and inflammation. While basophilia is most commonly associated with chronic myeloid leukemia (CML), it may also occur in rare subtypes of AML, most notably acute basophilic leukemia (ABL) and AML with basophilia. The latter can be further classified according to distinct genetic markers. The case that will be presented here is a patient with ABL with a concomitant biallelic inactivation of TP53. Accurately distinguishing between malignancies that present with basophilia is essential, as they may require different treatment approaches and carry markedly different prognoses. Methods/Case Report: This patient is a 58-year-old male with no significant prior medical history or family medical history who presented with severe pancytopenia. No peripheral blood basophilia was observed. However, bone marrow differential count showed 10% basophils and 30% myeloid blasts and some blasts showed basophilic granules. Flow cytometry of the bone marrow aspirate showed that the blasts expressed the following antigens: CD11b (subset dim), CD13 (dim), CD33 (dim and partial), CD34, CD36 (subset), CD38 (heterogenous), CD45 (dim), CD71, CD117, HLA-DR (heterogenous) and intracellular Myeloperoxidase (partial). Cytogenetic analysis of metaphase cells revealed one abnormal cell line with a complex hypodiploid composite karyotype: 42-45,XY,der(3) t(3;19)(q12;p13.1),-5,-7,+16,der(16)t(1;16)(p22;q24),der(16)t(7;16) (q11.2;q24),add(17)(p11.1), -19, add(19)(q12),+20,-22[cp19]/46,XY[1]. FISH detected TP53 gene deletion in 85% of nuclei. NGS study showed TP53 mutation with a VAF of 64.6%, but no other mutations. Therefore, the final classification is acute basophilic leukemia based on the 5th WHO classification or acute myeloid leukemia with mutated TP53 based on the 2022 International Consensus Classification. ABL with mutated TP53 and TP53 deletion has not been reported in the literature. The cytogenetic and molecular findings of biallelic inactivation of p53 genes provides insight on the prognosis of ABL and may also influence the treatment decision of ABL. Results: NA Conclusion: This case highlights a rare presentation of acute basophilic leukemia (ABL) with biallelic inactivation of TP53, a genetic alteration not previously reported in the literature. The diagnostic complexity of ABL - particularly in distinguishing it from chronic myeloid leukemia (CML) in blast crisis and AML with basophilia - underscores the importance of integrating morphologic features, immunophenotyping, cytogenetics, and molecular diagnostics. The immunophenotypic profile, in conjunction with distinct cytogenetic abnormalities and TP53 deletion/mutation, guided the final diasis. For pathologists, this case serves as a reminder of the diagnostic value in recognizing basophilic differentiation and correlating it with molecular findings. It also contributes new data to the limited literature on ABL, particularly in the context of TP53-driven pathogenesis. Ultimately, this case strengthens the role of precision diagnostics in improving classification, prognostication, and treatment planning for rare and aggressive hematologic malignancies.

Volume

164

Issue

Suppl 1

First Page

S108

Comments

American Society for Clinical Pathology (ASCP) Annual Meeting, November 17-20, 2025, Atlanta, GA

Last Page

S109

DOI

10.1093/ajcp/aqaf121.265

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