Terminal deletion of the long arm of chromosome 9 in acute promyelocytic leukemia with a cryptic PML/RAR alpha 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 alpha (RAR alpha)/PML fusion signal usually generated on the der(17) t(15;17). However, rearrangement of the RAR alpha gene and expression of the PML/RAR alpha chimeric transcript were identified by Southern blot and reverse transcriptase-polymerase chain reaction analyses, respectively. These results suggested that the PML/RAR alpha fusion gene was generated by submicroscopic interstitial insertion of the RAR alpha gene into the PML gene. Therefore, 9q- was interpreted as a secondary aberration following the PML/RAR alpha 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).