Cytogenetic profile of minimally differentiated (FAB M0) acute myeloid leukemia: correlation with clinicobiologic findings [see comments]

Abstract

Cytogenetic data were studied in 26 patients with de novo acute myeloid leukemia (AML) with minimal myeloid differentiation, corresponding to the M0 subtype of the French-American-British classification, in correlation with cytoimmunologic and clinical findings. Clonal abnormalities were detected in 21 cases (80.7%), 12 of which had a complex karyotype. Partial or total monosomy 5q and/or 7q was found, either as the sole aberration or in all abnormal metaphases, in 11 patients; in 8 cases, additional chromosome changes were present, including rearrangements involving 12p12–13 and 2p12–15 seen in 3 cases each. Five patients had trisomy 13 as a possible primary chromosome change; in 5 cases, nonrecurrent chromsome abnormalities were observed. Comparison of these findings with chromosome data from 42 patients with AML-M1 shows that abnormal karyotypes, complex karyotypes, unbalanced chromosome changes (-5/5q- and/or -7/7q- and +13) were observed much more frequently in AML-M0 than in AML-M1. Patients with abnormalities of chromosome 5 and/or 7 frequently showed trilineage myelodysplasia and low white blood cell count. Despite their relatively young age, complete remission was achieved in 4 of 11 patients only. Patients with +13 were elderly males with frequent professional exposure to myelotoxic agents. Unlike patients with clonal abnormalities, most AML-M0 patients with normal karyotype showed 1% to 2% peroxidase-positive blast cells at light microscopy and frequently achieved CR. It is concluded that (1) AML-M0 shows a distinct cytogenetic profile, partially recalling that of therapy-related AML, (2) different cytogenetic groups of AML-M0 can be identified showing characteristic clinicobiologic features, and (3) chromosome rearrangements may partially account for the unfavorable outcome frequently observed in these patients.

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“…The overall incidence of AML-M0 is similar to that in Western countries, which has been reported to be 0.1% to 9%. 3,8,10,11,[16][17][18][19] In this study, we confirmed that AML-M0 is a unique AML subtype, which showed higher incidence of organ infiltration and more frequent expression of CD7 and CD34, as well as complex cytogenetic changes of the leukemic cells than other AML subtypes. Although lg and TCR␤ gene rearrangements had been found in some AML-M0 cases, 8 all 10 patients tested in this study showed germline configuration of both genes, which was feasible to exclude lymphoid differentiation of the leukemic cells in these patients.…”

“…Similar findings had been reported from other institutions. 8,11,18 There were no specific chromosomal abnormalities in this subtype of AML. The common aberrations shown in this study as well as from literature, such as +8, −7/7q−, −5/5q−, can also be detected in other hematologic malignancies.…”

“…A low remission rate and poor prognosis after conventional chemotherapy in adult patients with AML-M0 has been reported, possibly because of the frequent occurrence of unfavorable cytogenetic abnormalities, expression of immature surface antigens and multidrug resistance-associated membrane protein. [6][7][8][9][10][11] So far, no comprehensive studies on pediatric patients with AML-M0 have been reported and there have been very few data in the literature concerning age distribution of this subtype of leukemia. The clinical and biological differences between AML-M0 patients who are responsive to chemotherapy and those who are not are also not clear.…”

Acute myeloid leukaemia M0: haematological, immunophenotypic and cytogenetic characteristics and their prognostic significance: an analysis in 241 patients

“…This makes assessment of the presence of dysplastic features difficult. Multilineage dysplasia in AML M0, however, has been described (Cuneo et al , 1995; Lemež et al , 1998), which may suggest a stem cell dysfunction in AML M0.…”

Trisomy 13 and myeloid malignancy — characteristic blast cell morphology: a United Kingdom Cancer Cytogenetics Group survey

“…Cohen et al (1998 ) found no distinguishing features of blasts in AML M0; two‐thirds of patients had blasts with cytoplasmic vacuoles, but none had cytoplasmic budding. Trisomy 13 was found in 5/26 patients with AML M0 ( Cuneo et al , 1995 ); 4/34 adults with AML expressing lymphoid markers had +13 or structural aberrations of 13q ( Cuneo et al , 1992), and 2/17 AML M0 patients had +13 and 1/17 had tetrasomy 13 ( Cohen et al , 1998 ). A high proportion of karyotypically normal cells was observed in our patients.…”