A NONCLASSICAL TRANSLOCATION INVOLVING 17Q12 (RETINOIC ACID RECEPTOR-ALPHA) IN ACUTE PROMYELOCYTIC LEUKEMIA (APML) WITH ATYPICAL FEATURES

Acute promyelocytic leukemia (APML) almost always involves a chromosom al translocation t(15;17) that results in the fusion of the retinoic a cid receptor cu (RAR alpha) gene with a transcription factor gene call ed PML. Several cases of APML with t(11;17) have recently been describ ed, involving fusion of the RAR alpha gene with a new zinc finger gene named PLZF. We report here a second non-classical translocation, t(5; 17), with a rearranged RAR alpha gene in a child with APML. Based on r estriction endonuclease analysis, the rearrangement of RARA alpha occu rred within the second intron, the common breakpoint site for t(15;17) . The leukemic cells in the bone marrow aspirate were a mixture of hyp ergranular and hypogranular bilobed promyelocytes. Although less than 1% abnormal promyelocytes were identified after induction therapy, cyt ogenetics revealed persistent t(5;17). Therefore, the child was treate d with all-trans-retinoic acid (ATRA). There was no disease progressio n, and one marrow was interpreted as remission, with confirmation by c ytogenetics which failed to reveal the translocation. However, disease reoccurred shortly after completion of ATRA. This poor response to AT RA may be an additional characteristic associated with non-classical t ranslocations in APML. The identification of a second variant transloc ation involving the RAR alpha gene in APML suggests yet another RAR al pha rearrangement related to neoplastic myelopoiesis.