Cancer genetics · 2026
Cytogenomic landscape of adult Philadelphia chromosome-positive acute lymphoblastic leukemia in Malaysia.
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Phan Chin Lee, Zakaria Zubaidah, Yegappan Subramanian, Khang Tsung Fei, Ng Ching Ching
Аннотация
BACKGROUND: Philadelphia chromosome-positive acute lymphoblastic leukemia (-Ph+ ALL) is a high-risk leukemia often accompanied by additional genomic abnormalities beyond BCR::ABL1.
METHODS: We analyzed 74 newly diagnosed adult -Ph+ ALL patients. Additional chromosomal abnormalities (ACAs) were assessed by conventional cytogenetics in 51 patients and copy number variations (CNVs) by combined array comparative genomic hybridization plus single nucleotide polymorphism (array-CGH+SNP) in 43 patients.
RESULTS: ACAs were detected in 31 cases (60.8%), including complex karyotypes in 11 (35.5%). CNVs were identified in 38 cases (88.4%) and were predominantly deletions (69.2%). Recurrent abnormalities included double Ph chromosome, monosomy 7, chromosomal gains at 8q, 9q34, 22q11, and losses at 7p, 9p, and 20q. The t(3;9;22) was the most frequent t(9;22) variant (12.9%), despite being rare in previous studies of adult Ph+ ALL. IKZF1 deletions were most frequent (91.7%), followed by CDKN2A/B (44.4%), PAX5 (38.9%) and RB1 (30.6%). IKZF1 co-deletions with CDKN2A/B and/or PAX5 occurred in 66.7%. IKZF1 and 22q11.22 co-deletions occurred in 34.2%, and VPREB1 deletions in 15.8%; both have been associated with adverse outcomes in ALL. Copy-neutral loss of heterozygosity >5 Mb was detected in 16.3%, frequently involving chromosome 9p and encompassing the CDKN2A/B loci.
DISCUSSIONS: Adult Ph+ ALL in this multi-ethnic cohort exhibited marked genomic heterogeneity, with frequent submicroscopic alterations detectable only through integrated genomic profiling. Comprehensive genomic characterization is needed to better understand leukemogenesis and refine risk stratification.
METHODS: We analyzed 74 newly diagnosed adult -Ph+ ALL patients. Additional chromosomal abnormalities (ACAs) were assessed by conventional cytogenetics in 51 patients and copy number variations (CNVs) by combined array comparative genomic hybridization plus single nucleotide polymorphism (array-CGH+SNP) in 43 patients.
RESULTS: ACAs were detected in 31 cases (60.8%), including complex karyotypes in 11 (35.5%). CNVs were identified in 38 cases (88.4%) and were predominantly deletions (69.2%). Recurrent abnormalities included double Ph chromosome, monosomy 7, chromosomal gains at 8q, 9q34, 22q11, and losses at 7p, 9p, and 20q. The t(3;9;22) was the most frequent t(9;22) variant (12.9%), despite being rare in previous studies of adult Ph+ ALL. IKZF1 deletions were most frequent (91.7%), followed by CDKN2A/B (44.4%), PAX5 (38.9%) and RB1 (30.6%). IKZF1 co-deletions with CDKN2A/B and/or PAX5 occurred in 66.7%. IKZF1 and 22q11.22 co-deletions occurred in 34.2%, and VPREB1 deletions in 15.8%; both have been associated with adverse outcomes in ALL. Copy-neutral loss of heterozygosity >5 Mb was detected in 16.3%, frequently involving chromosome 9p and encompassing the CDKN2A/B loci.
DISCUSSIONS: Adult Ph+ ALL in this multi-ethnic cohort exhibited marked genomic heterogeneity, with frequent submicroscopic alterations detectable only through integrated genomic profiling. Comprehensive genomic characterization is needed to better understand leukemogenesis and refine risk stratification.