Terminal Deletion of the Long Arm of Chromosome 9 in Acute Promyelocytic Leukemia with a Cryptic PML/RARα Rearrangement

Deletions of the long arm of chromosome 9 (9q−) are rare aberrations specifically found in acute myeloid leukemia (AML). Here we describe the first case of acute promyelocytic leukemia (APL) with a terminal 9q deletion as a sole abnormality. Chromosome analysis of the bone marrow cells showed 46,XX,del(9)(q22) in all 20 metaphases. Fluorescence in situ hybridization (FISH) analysis with painting probes of chromosomes 15, 17, and 9 revealed only two normal chromosomes 15 and 17, normal chromosome 9, and del(9)(q22). FISH with cosmid DNA probes flanking the breakpoints of t(15;17) did not show the retinoic acid receptor α (RARα)/PML fusion signal usually generated on the der(17)t(15;17). However, rearrangement of the RARα gene and expression of the PML/RARα chimeric transcript were identified by Southern blot and reverse transcriptase-polymerase chain reaction analyses, respectively. These results suggested that the PML/RARα fusion gene was generated by submicroscopic interstitial insertion of the RARα gene into the PML gene. Therefore, 9q− was interpreted as a secondary aberration following the PML/RARα rearrangement. The patient died during induction therapy because of intracerebral hemorrhage. Considering other reported cases of APL with 9q−, 9q− may be an adverse prognostic factor in APL as observed in AML with t(8;21).