To explore the genetic basis for a rare case of acute B-lymphocytic leukemia (B-ALL) with double Philadelphia chromosomes (Ph) and double derivative chromosome 9s [der(9)].
A patient with double Ph and double der(9) B-ALL who presented at Shanghai Zhaxin Intergrated Traditional Chinese and Western Medicine Hospital in June 2020 was selected as the subject. Bone marrow morphology, flow cytometry, G-banding karyotyping, fluorescence in situ hybridization (FISH), genetic testing and chromosomal microarray analysis (CMA) were used to analyze bone marrow samples from the patient at various stages.
At initial diagnosis, the patient’s bone marrow morphology and flow immunotyping have both supported the diagnosis of B-ALL. G-banded karyotyping of the patient indicated double Ph, in addition with hyperdiploid chromosomes involving translocations between chromosomes 9 and 22. BCR-ABL1 fusion gene was positive. Genetic testing at the time of recurrence revealed presence of a heterozyous c.944C>T variant in the kinase region of the ABL1 gene. FISH showed a signal for ABL1-BCR fusion on both chromosome 9s. CMA showed that the mosaicism homozygosity ratio of chromosome 9 was about 40%, and the mosaicism duplication ratio of chromosome 22 was about 43%.
Since both der(9) homologs were seen in 40% of cells, the possible mechanism for the double der(9) in this patient may be similar to that of double Ph, which might have resulted from non-disjunction during mitosis in the Ph chromosome-positive cell clone.