Acute promyelocytic leukemia after treatment for non-Hodgkin's lymphoma with drugs targeting topoisomerase II.

We report a patient who developed acute promyelocytic leukemia (APL) concomitantly with a second relapse of non-Hodgkin's lymphoma (NHL), intermediate grade, WF type E. At diagnosis and at first NHL relapse, the patient had received the same chemotherapy regimen, which included drugs targeting DNA topoisomerase II, i.e., etoposide (total dose 5,760 mg) and idarubicin (total dose 180 mg). Thirty-eight months after initial treatment, the patient showed pancytopenia associated with lymphoma recurrence. Bone marrow examination revealed the presence of atypical promyelocytes with Auer rods; cytogenetics showed t(15;17), and molecular analysis detected promyelocytic leukemia-retinoic acid receptor alpha rearrangement. APL reached complete remission after all trans retinoic acid therapy, whereas NHL did not respond to further chemotherapy. In the literature, five other patients developed APL after treatment for lymphoma, from a total of 59 patients developing sAPL after treatment for any type of neoplasia.

Consistent amounts of acute leukemia-associated P190BCR/ABL transcripts are expressed by chronic myelogenous leukemia patients at diagnosis.

In chronic myelogenous leukemia (CML), the Philadelphia (Ph) chromosome translocation results in the formation of BCR/ABL genes, normally transcribed in two types of hybrid transcripts with a b2a2 or b3a2 BCR/ABL junction, which give origin to 210-kD fusion proteins (P210). A third type of BCR/ABL (with e1a2 type of junction) has been identified in approximately 50% of the Ph-positive acute lymphoblastic leukemia (Ph+ALL) cases and results in the production of a BCR/ABL protein of 190 kD (P190). The presence of this transcript has been associated almost exclusively with the presence of an acute leukemia phenotype. By contrast, here we describe that in addition to transcripts with the b2a2 and b3a2 types of junction corresponding to the P210 proteins, virtually all CMLs at diagnosis bear also BCR/ABL transcripts showing the e1a2 type of junction, which correspond to the acute leukemia-associated P190 protein. With a quantitative polymerase chain reaction assay we found that the amount of the e1a2 mRNA present in CMLs in chronic phase, although in absolute amount much lower than that present in Ph+ ALLs, represents in most cases approximately 20% to 30% of the total BCR/ABL transcripts. Moreover, using a novel and very sensitive Western blot technique, we detected relevant amounts of P190 protein in addition to P210 from peripheral cells of two of the patients.