Acquired Philadelphia chromosome with transformed myelodysplastic syndrome

Transformation to acute myeloid leukemia (AML) frequently occurs in patients with myelodysplastic syndrome (MDS), and genetic evolution probably plays a critical role in this transformation. However, late appearance of the Philadelphia (Ph) chromosome during the course of transformed MDS is extremely rare. We report a 77-year-old man with transformed MDS and an acquired Ph chromosome. He was initially diagnosed with refractory anemia with 45,XY,del(5)(q?),-7,-14,-17,+mar1,+mar2 (7/20) as the major clone. After 4 months, hematological studies showed progression of anemia with increased number of blast cells. Conventional chromosome analysis revealed 45,XY,del(5)(q?),-7, t(9;22)(q34;q11.2),-14,-17,+mar1,+mar2 (20/20), a subclone with an acquired Ph chromosome derived from a stem clone observed at MDS diagnosis. RT-PCR results were positive for major BCR- ABL transcript. Although a comparison of whole-genome sequences between original and transformed clones would be informative, the acquired Ph chromosome probably played a role as a "class-I mutation," which increases cell proliferation in transformed MDS.