Publication Only: Acute myeloid leukemia - Biology & translational research
Using conventional cytogenetics, an abnormal karyotype can be detected in ˜60% of adult acute myeloid leukemia (AML) patients. Taking into consideration the identified cytogenetic abnormalities AML patients are currently classified into three risk groups: favorable, intermediate and adverse. These genetic abnormalities are the most important factors in determining response to chemotherapy as well as outcome in AML. Recently, a new cytogenetic category was introduced, namely, monosomal karyotype (MK) defined by the presence of two or more distinct autosomal monosomies (AM) or a single AM associated with one or more structural abnormalities (excluding core-binding factor AML and acute promyelocytic leukemia). The most common monosomies involved in MK+ AML are -5 and -7. The mechanisms responsible for MK+ AML are still unclear, but it may be associated with deletions or mutations in TP53 gene and multiple drug resistance. In fact, recent evidence indicated that TP53 alterations occur in 70% of MK+ AML patients.
Aim of this study was to determine frequency of MK in adult patients with AML and to detect the most common monosomies involved in MK+ AML.
Cytogenetic investigations of bone marrow and/or peripheral blood cells from 116 newly diagnosed adult patients with AML (range: 18-85 years) were performed. The methods of conventional cytogenetics (GTG) and fluorescence in situ hybridization (FISH) were used. Cytogenetic methods were performed using standard techniques and karyotypes were described according to the International System for Human Cytogenetic Nomenclature.
Cytogenetic investigations were performed in 116 newly diagnosed patients with AML. Chromosomal aberrations of various kinds were found in 68 (59%) cases, which is comparable to the data reported in the literature. Taking into consideration the identified cytogenetic abnormalities patients were classified by risk groups according to the European LeukemiaNet criteria: the group of patients with favorable cytogenetic markers, the intermediate-risk group without significant prognostic markers and the group of patients with adverse prognosis factors. Of 116 patients with AML, MK was found in 7 (6%) cases. With respect to the distribution of monosomies in MK, 2 (29%) cases had one AM and 5 (71%) had 3 or more AM. The most common monosomies involved in MK+ AML were: -5 (71%), -16 (57%), -7 (43%) and -17 (43%). Of 7 patients with MK+ AML, one (14%) had only monosomies, whereas other 6 (86%) - had also structural cytogenetic abnormalities, except for monosomies. Spectrum of additional structural chromosomal aberrations associated with MK was as follows: del(6)(q13), del(13)(q11q22), t(7;14)(q11;q21), t(10;18)(p12;q12), t(15;17)(p11;q12), t(12;18)(p12;q12), add(2)(q36), add(12)(p13), add(16)(q12-13), marker and ring chromosomes and acentric structures. Three patients, except for abnormal ones, had normal metaphases in their karyotypes. The patients with MK+ AML were classified to the new cytogenetic category of AML with a very poor prognosis, even after allogeneic stem cell transplantation.
In our investigation frequency of MK in adult patients with AML was 6%. Of the MK+ AML cases, 14% patients had only monosomies, whereas 86% patients had also structural cytogenetic abnormalities, except for monosomies. The most common monosomies were: -5 (71%), -16 (57%), -7 (43%) and -17 (43%). The patients with MK+ AML were classified to the subgroup of AML with a very poor prognosis.