Cytogenetic characteristics of therapy‐related acute nonlymphocytic leukaemia, preleukaemia and acute myeloproliferative syndrome: correlation with clinical data for 61 consecutive cases

Abstract

Cytogenetic studies were performed on a new series of 23 patients with therapy-related acute non-lymphocytic leukaemia, preleukaemia or an acute myeloproliferative syndrome. In our total series of now 61 cases studied by chromosome banding techniques, at least one of the abnormalities -7, 5q-, 7q- or -5 or some related unbalanced translocations, primarily -7, +t(1q7p), was observed in 40 patients. The critical region for the deletions of chromosome no. 5 comprises bands 5q22 to 5q33 and of chromosome no. 7 bands distal to 7q22. The third most frequently involved chromosome was no. 21, rearranged at band 21q22 in the three patients with 21q+ and in one patient with 21q-. An i(21q) was observed in two patients, a -21 in four patients and a -22, +t(21q22q) and a -5, -21, +t(5p21q) in one patient each. Other characteristic abnormalities included total loss or rearrangements of the short arm of chromosome no. 17, observed in nine patients. One patient had a -12, three others had rearrangements resulting in a partial or total loss of the short arm of chromosome no. 12. A 19q+ with translocation to band 19q13 was observed in three cases, a -18 in three cases and a 3p- in four cases. Thirty-one patients with multiple chromosome aberrations experienced a significantly shorter survival as compared to 13 patients with a normal karyotype (P = 0.02) and 17 patients with one single chromosome aberration (P less than 0.01).

Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976–1993 and on 5098 unselected cases reported in the literature 1974–2001

“…In the majority of other reports, the percentages of previous non-neoplastic diseases have generally been lower, varying from 2 to 13%. [6][7][8][9]16,19,[44][45][46][47][48][49][50] The pooled analysis of the cytogenetic features of t-AML/t-MDS, including data from unselected series in the literature, 32 revealed several significant differences between treatmentrelated and de novo disorders (Tables 2 and 3). In t-AML/t-MDS, the number of anomalies and the ploidy levels differed from de novo cases, with complex karyotypes and hypodiploidy being more common in t-AML/t-MDS.…”

Increased frequency of dicentric chromosomes in therapy-related MDS and AML compared to de novo disease is significantly related to previous treatment with alkylating agents and suggests a specific susceptibility to chromosome breakage at the centromere

“…[11][12][13][14][15][16][17][18][19][20][21][22][23][24] More recently, the DNA topoisomerase II inhibitors have also been shown to be leukemogenic, in most instances administered in combination with platinum derivatives or an alkylating agent. [25][26][27][28] These leukemias primarily present balanced translocations to chromosome bands 11q23 or 21q22 29 with rearrangement of the MLL and the AML1 genes, but also less frequently other balanced rearrangements such as the inv (16)(p13q22), and the t(15;17)(q22;q11) known from de novo MDS and AML.…”

“…One hundred and eighty consecutive cases of t-MDS and t-AML for which the cytogenetic and clinical characteristics have been published previously in detail, [11][12][13][14][15][16][17] and a further 231 consecutive cases of de novo MDS and AML studied at our laboratory by conventional G-banding chromosome analysis of bone marrow cells, were re-analyzed. The cytogenetic nomenclature of ISCN (1995) was used.…”

Secondary acute myeloid leukaemia with 7q- complicating azathioprine treatment for rheumatoid arthritis.

“…'3 Thus, 7q-/-7 can be considered a characteristic finding in secondary leukaemia. '3 14 A detailed examination of the drug history of this patient revealed three candidate causative drugs: myocrisin, penicillamine and azathioprine. Although myocrisin and penicillamine cause myelosuppression and aplastic anaemia, no case of secondary leukaemia or malignancies has been attributed to their use.…”