CORRELATION OF CYTOGENETIC FINDINGS WITH CLINICAL-FEATURES IN 18 PATIENTS WITH INV(3)(Q21Q26) OR T(3,3)(Q21,Q26)

An inversion in the long arm of chromosome 3 - inv(3)(q21q26)- or a tr anslocation between both homologous chromosomes 3 - t(3;3)(q21;q26) - is found specifically in myeloid neoplasias characterized by disturban ces of thrombopoiesis and megakaryocyte development. Cytogenetic findi ngs were correlated with clinical and hematological data in altogether 18 patients with acute nonlymphocytic leukemia (ANLL) and with inv(3) (13 patients) or t(3;3) (five patients), six of whom were male and 12 who were female. Chromosomal changes in addition to the 3q anomalies were demonstrated in 14 out of 18 patients, predominantly numerical an d structural aberrations of chromosome 7 (12 cases) and/or abnormaliti es of 5q (five cases). Complex karyotype abnormalities were observed i n six of 13 patients with inv(3), but in only one of five patients wit h t(3;3). In ten out of our 18 patients a preceding myelodysplastic sy ndrome (MDS) and/or exposure to mutagenic/carcinogenic agents had been established. In eight patients the morphology of ANLL blasts was imma ture (FAB subtype M1); in three patients ANLL-M4, and in two patients each ANLL-MS, M6, and M7 was diagnosed; in one patient with antecedent MDS the leukemic blasts were not classifiable according to the FAB cr iteria. A disturbed megakaryocyte development, characterized by an exc ess of micromegakaryocytes was observed in 14 patients, seven of them showed normal or elevated platelet counts as an unusual feature in pat ients with ANLL. The clinical course and outcome was extremely poor: 1 5 of 18 patients died within 10 months after the diagnosis of ANLL. Be cause of their missing response to conventional chemotherapy, patients with inv(a) or t(3;3) have to be estimated as at high risk. The chara cterization of genes affected by inv(3) or t(3;3) could help to elucid ate molecular changes leading to impaired proliferation and differenti ation of hematopoietic cells, also of the megakaryocytic lineage. Base d on molecular genetic findings new therapeutical approaches could be designed.