To the editor : Chromosome 19 abnormalities are commonly seen in AML , M 7

A recent paper by Dastugue et al1 reported the cytogenetic profile of 53 patients with acute megakaryoblastic leukemia (FAB-M7). The authors studied 30 children and 23 adults evaluated by the Groupe Français de Cytogénétique Hématologique, and identified 9 different groups based on their conventional cytogenetic analysis. These groups reflect, in part, the known association of M7 leukemia with Down syndrome, with the t(1;22) translocation, 3q21 or q26 translocations, and with the Philadelphia chromosome [t(9;22)]. No new recurrent abnormalities were identified, although mapping of breakpoints identified possible rearrangement hot spots involving 17q, 11q, 21q, and 16q. Table 1 in their manuscript showed 7 patients with trisomy 19, 1 patient with a hyperdiploid karyotype and an extra copy of chromosome 19, 1 patient with loss of 19, 1 patient with add(19)(p13), and 1 patient with a t(4;19) (p12;?) translocation. In 2001, we reported the frequent gain of chromosome 19 in megakaryoblastic leukemias using comparative genomic hybridization (CGH).2 We used CGH and G banding to analyze both primary patient samples and megakaryoblastic cell lines, and we found chromosome 19 abnormalities in 4 patients by CGH that we could not identify by G banding. Four of 12 patient samples analyzed demonstrated trisomy 19 ( 19q13), with 2 of 4 acute megakaryoblastic leukemia–M7s (AML-M7s) and 2 of 8 secondary acute leukemias, which occurred after a myeloproliferative disorder, demonstrating this abnormality. In addition, 9 of the 11 megakaryocytic leukemia cell lines that we analyzed showed gain of 19 or 19q by CGH. The larger study by Dastugue et al identified an approximately 20% incidence of chromosome 19 abnormalities with trisomy 19 occurring in 8 (16%) of 50 patients lacking the Philadelphia chromosome. The presence of this abnormality in 8 of 9 cytogenetic subgroups suggests its commonality in this disease process. Little emphasis was placed on this finding in their discussion and our studies suggest that the true incidence of trisomy (or amplification) of chromosome 19 could be even higher, if more sensitive studies such as comparative genomic hybridization or spectral karyotyping (SKY) are performed. This may be especially true in the adult group, as 6 (26%) of 23 adult patients had marker chromosomes, which could contain chromosome19 material, as we found to be the case in the M7 cell lines that we analyzed. The 19q13 region is gene rich and includes the AKT2, cyclin E, and MLL2 genes, among others. These particular candidate genes have been implicated in solid tumors and are under investigation in hematologic malignancies as well. We believe the Dastugue study provides further support for investigating the role of chromosome 19 abnormalities in the megakaryoblastic leukemias.