Hypodiploidy with < 40 chromosomes is associated with poor prognosis in B cell precursor
acute lymphoblastic leukemia. In some patients, the hypodiploid clone undergoes endoreduplication, resulting in doubling of the number of chromosomes and masquerades as a high hyperdiploid BCP-ALL. Karyotyping reveals metaphases with 50-79 chromosomes masking the hypodiploid clone. Identifying hypodiploidy in such cases requires awareness of non random alterations of chromosomal copy numbers found in hypodiploid BCP-ALL. We used a systematic strategy to identify masked hypodiploidy integrating targeted fluorescence in situ hybridization (FISH) analysis directed towards identifying
monosomies of chromosomes 7, 15 and 17 and flow cytometry-based ploidy analysis (
FCPA). Of 445 patients diagnosed as BCP ALL, 2.9% (13/445) were classified as hypodiploid including patients with masked hypodiploidy. Karyotype analysis showed hypodiploidy in 3 patients, near
triploidy in 4 patients and normal karyotype in 6 patients. Four patients with near
triploid clone on karyotype showed either bimodal peak (2 patients) or single low hypodiploid peak (1 patient) or only near
triploid peak (1 patient) on
FCPA. All 6 patients with normal karyotype revealed either bimodal peak (4 patients) or hypodiploid peak (2 patients) on
FCPA. Targeted FISH analysis unmasked hypodiploid clone showing
monosomies of chromosomes 7, 15 and 17 in all ten patients. Our algorithm successfully identified masked hypodiploidy in patients, including those with endoreduplication (4 patients) and normal karyotype (6 patients). Integrating
FCPA with targeted FISH analysis provides a practical, sensitive and specific approach to identify masked hypodiploidy in low resource settings.