Molecular genetic characterization of Philadelphia chromosome-positive acute myeloid leukemia. (January 2023)

• Record Type: Journal Article
• Authors: Zhou, Qianghua; Zhao, Davidson; Eladl, Entsar; Capo-Chichi, Jose-Mario; Kim, Dennis Dong Hwan; Chang, Hong
• Is Part Of: Leukemia research. Volume 124(2023)
• Publication Date: 2023-01
• Subjects: Ph+ AML -- Molecular cytogenetics -- NGS -- Clinical outcomes; Ph Philadelphia chromosome -- AML acute myeloid leukemia -- CML chronic myelogenous leukemia -- NGS next-generation sequencing; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2022.107002
• Languages: English
• ISSNs: 0145-2126

Abstract

Abstract: Background: Philadelphia chromosome-positive acute myeloid leukemia (Ph+ AML) is a provisional disease entity in the 2016 WHO classification, while its genetic profile of Ph+ AML remains poorly defined. In addition, the differentiating features of Ph+ AML and chronic myeloid leukemia in myeloid blast crisis (CML-MBC) remain controversial. Methods: We conducted a retrospective study of 15 Ph+ AML patients to compare their clinical and laboratory profiles with 27 CML-MBC patients. Results: Compared to CML-MBC, Ph+ AML patients presented with significantly higher peripheral WBC count and bone marrow blast percentage. The immunophenotypic profiles were largely similar between Ph+ AML and CML-MBC, except for CD4 expression, which was significantly enriched in CML-MBC. Ph+ AML patients less frequently harboured co-occurring additional cytogenetic abnormalities (ACA) compared to CML-MBC, and trisomy 19 (23%) and IDH1/2 (46%) were the most common ACA and mutated genes in Ph+ AML, respectively. Overall survival (OS) did not significantly differ between Ph+ AML and CML-MBC. Ph+ AML without CML-like features appeared to have a better outcome compared to Ph+ AML with CML-like features; ACA in Ph+ AML may confer an even worse prognosis. Conclusions: Our results indicate that patients with Ph+ AML share similar genetic profiles and clinical outcomes with those with CML-MBC, thus should be classified as a high-risk entity. Highlights: Ph+ AML occurs in a predominantly older male population and exhibits higher white blood cell counts and bone marrow blast percentages. Ph+ AML frequently harbors IDH1/2 mutations. Ph+ AML has similar adverse overall survival compared with CML-MBC and the survival outcomes are even worse if presenting with additional cytogenetic abnormalities or CML-like features.