Single monosomy as a relatively better survival factor in acute myeloid leukemia patients with monosomal karyotype

Abstract

on behalf of the Korean Society of Hematology AML/MDS Working Party Monosomal karyotype (MK) defined by either ⩾ 2 autosomal monosomies or single monosomy with at least one additional structural chromosomal abnormality is associated with a dismal prognosis in patients with acute myeloid leukemia (AML). It was detected in 174 of 3041 AML patients in South Korean Registry. A total of 119 patients who had received induction therapy were finally analyzed to evaluate the predictive factors for a positive prognosis. On multivariate analysis, single monosomy, the absence of abn(17p), ⩾ 10% of cells with normal metaphase and the achievement of a complete remission (CR) after induction therapy were significant factors for more favorable outcomes. Especially, single monosomy remained as a significantly independent prognostic factor for superior survival in both patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR and who did not. Allo-HSCT in CR improved overall survival significantly only in patients with a single monosomy. Our results suggest that MK-AML may be biologically different according to the karyotypic subtype and that allo-HSCT in CR should be strongly recommended to patients with a single monosomy. For other patients, more prudent treatment strategies should be examined. Furthermore, the biological mechanism by which a single monosomy influences survival should be investigated. ( Blood Cancer Journal INTRODUCTIONAlthough several different cytogenetic classifications exist for acute myeloid leukemia (AML), it has been generally agreed that specific cytogenetic abnormalities result in unfavorable prognoses. Adverse cytogenetic risk factors include − 5/5q deletion (del (5q)), − 7/7q deletion (del(7q)), − 17/17p abnormality (abn(17p)), inv(3)(q21q26/t(3;3)(q21;q26) and complex karyotype (CK).

The impact of concomitant cytogenetic abnormalities on acute myeloid leukemia with monosomy 7 or deletion 7q after HLA‐matched allogeneic stem cell transplantation

“…The 2-year cumulative incidence of relapse was 36.7% for the "-7/7q-± CK group," 47.8% for the "MK group," 51% for the "-5/5qgroup," 62.9% and 68.4% for the "inv(3) group" (P < .001, Figure 2A), which translated into a 2-year probability of LFS of 48%, 36.4%, 28.4%, 19.1% and 17.3% for the "-7/7q-± CK," "MK," "-5/5q-," "abn(17p)" and "inv(3)" groups, respectively (P < .001, Figure 2C). The 2-year NRM was similar across our five cytogenetic <.0001 20 (16)(17)(18)(19)(20)(21)(22)(23)(24) .99 23 (18)(19)(20)(21)(22)(23)(24)(25)(26)(27) <.0001 27 (22)(23)(24)(25)(26)(27)(28)(29)(30)(31) <.0001 13 (10)(11)(12)(13)(14)(15)(16) <.0001 26 (22)(23)(24)(25)(26)(27)(28)(29)…”

“…14,15 Within MK, the presence of monosomy 7 alone did not show any independent impact on survival. 14,16 However, in the transplant setting, a retrospective study from the EBMT addressing SCT for MK AML showed that monosomy 7 retained a significant impact on outcomes. 17 We recently reported the outcome of 125 patients with AML and 17p abnormalities (abn(17p)) transplanted in first remission.…”

Mutations of myelodysplastic syndromes (MDS): An update

“…A single monosomy has resulted in better prognosis and PFS, and thus, remained as a significantly independent prognostic factor for patients both treated or untreated with allo-HSC transplantation [127]. However, biological mechanism of single MK could be different from 2 or more MK, which needs further evaluation on both AML and MDS.…”

<p>Chromosomal Instability in Farmers Exposed to Pesticides: High Prevalence of Clonal and Non-Clonal Chromosomal Alterations</p>

“…70,71 In fact, a linear trend between CAs in PBLs and subsequent cancer risk has been shown by several prospective cancer studies. 29,[72][73][74][75] CEP2,CEP8,CEP11 CEP3,CEP15,CEP17 Exposed Unexposed Figure 5 Representative FISH images of an exposed and an unexposed individual. Metaphase spreads are shown and boxes indicate representative interphase nuclei for each case.…”