3q21 and 3q26 cytogenetic abnormalities in acute myeloblastic leukemia: biological and clinical features

Background and Objective. Acute myeloblastic leukemia (AML) with features o f myelodysplastic syndrome (MDS) and abnormalities of megakaryocytopoiesis is often characterized by cytogenetic aberrations of the 3q21 and 3q26 band s involving inv(3)(q21q26) and (3;3)(q21;q26). These aberrations have been described in all FAB subtypes with the exception of M3, and in MDS and in m egakaryoblastic crisis of chronic myeloid leukemia. We reviewed the biologi cal and clinical features of 10 cases of AML with inv(3)(q21q26) and t(3;3) (q21;q26). Design and Methods. Four hundred and sixteen patients with AML were studied in our Institute by cytogenetic analysis and 10 (2.4%) showed inv(3)(q21q2 6) (7 patients) or t(3;3)(q21;q26) (3 patients): 7 males, 3 females; median age, 43.5 yrs. We also used RT-PCR to investigate the pattern of expressio n of the EVI-1 gene in 5 patients. Results. Additional chromosomal changes were demonstrated in 6 patients. In 5/10 cases a preceding MDS had been observed. A possible occupational expo sure was established in 2 patients (a farmer and an histologist employing o rganic solvents) and another patient had a therapy-related leukemia. AML su btype was M1 in 9 patients and M2 in 1. A variable excess of micromegakaryo cytes was observed in all the patients. In 5 patients the platelet count wa s normal or Increased (median number: 172.5x10(9)/L; range 55-440). Express ion of EVI-1 gene was present in all the 5 patients studied. The clinical c ourse and outcome was extremely poor: 9/10 patients were resistant and 1 pa tient showed a partial remission after induction therapy. Of the 9 patients resistant to the first line chemotherapy, 7 were also resistant to the sec ond line chemotherapy. Three patients obtained a morphologic complete remis sion after third line chemotherapy (duration 1, 3 and 6 months); 2 of them were submitted to autologous bone marrow transplantation, but relapsed afte r 1 and 3 months. The median overall survival was 5.5 months. Interpretation and Conclusions. Our findings evidence a strong correlation between 3q21q26 chromosomal aberrations, abnormalities of megakaryocytopoie sis and lack of response to conventional chemotherapy and support the diagn ostic and prognostic relevance of chromosome characterization in the classi fication of AML. (C)1999, Ferrata Storti Foundation.