Classical and molecular cytogenetic abnormalities and outcome of childhood acute myeloid leukaemia: report from a referral centre in Israel

Abstract

Summary The incidence of cytogenetic abnormalities in childhood de novo acute myeloid leukaemia (AML) and its prognostic significance was assessed in an Israeli paediatric referral centre. Cytogenetic analysis was successful in 86 of 97 children (<20 years of age) diagnosed between 1988 and 2002 with de novo AML. Fluorescence in situ hybridization analysis detected new information in 11 of them, leading to reassignment in cytogenetic group classification. The incidence of the various cytogenetic subgroups was as follows: normal – 9%; t(11q23) – 22%; t(8;21) – 13%; t(15;17) – 8%; inv(16) – 3·4%; abn(3q) – 4·6%; 7/7q‐(sole or main) – 5·8%; del(9q)(sole) and +21(sole) – 4·6% each; t(8;16) – 2·3%; t(6;9), t(1;22), +8(sole) – 1·1% each; and miscellaneous – 18%. The overall survival (OS) and event‐free survival (EFS) (4 years) for 94 patients treated with the modified Berlin‐Frankfürt‐Münster (BFM) AML protocols (non‐irradiated) were 59·9% (SE = 5%) and 55·7% (SE = 5%), respectively, and for the favourable t(8;21), t(15;17) and inv(16), OS was 60% (SE = 15%), 83% (SE = 15%) and 100% respectively. For the normal group it was 62% (SE = 17%), miscellaneous 64% (SE = 12%), t(11q23) 44·6% (SE = 11%) and of the −7/7q‐, del(9q)(sole) or t(6;9), none had survived at 4 years. The incidence of cytogenetic subgroups in the Israeli childhood AML population and their outcome were similar to other recently reported paediatric series. Cytogenetic abnormalities still carry clinical relevance for treatment stratification in the context of modern chemotherapy.

Prognostic significance of additional cytogenetic aberrations in 733 de novo pediatric 11q23/MLL-rearranged AML patients: results of an international study

“…43 Only some studies have specifically shown a correlation between complexity of the karyotype and outcome in pediatric AML. 2,6,14,33,44 EFS rates for patients with complex karyotype have ranged from 29% to 42% in these studies, which is comparable with the EFS obtained in our study. Alternatively, a strong negative association between monosomal karyotype, defined as a karyotype with at least 2 monosomies or 1 monosomy combined with at least 1 structural aberration, and outcome was described in adult AML.…”

Targeting DOT1L and HOX gene expression in MLL-rearranged leukemia and beyond

“…The survival rate of infant leukemias with MLL1 translocations remains low (approximately 50% with worse out come for the youngest patients) even with intensive chemotherapies and allogeneic hematopoietic stem cell transplantation [33–35]. The World Health Organization (WHO) classifies myeloid leukemias with 11q23 abnormalities as one group, with an estimated 4-year event free survival of 24–55% [16, 18, 36]. The unmet clinical problem presented by MLL1 -rearranged leukemias emphasizes the need for novel therapeutic strategies targeting these difficult-to-treat hematopoietic malignancies.…”

Molecular Identification of a New Splicing Variant of the <b><i>MLL</i></b>-<b><i>MLLT11</i></b> Fusion Transcript in an Adult with Acute Myeloid Leukemia and t(1;11)(q21;q23)

“…We attempted to summarize these published data in order to evaluate the characteristics of these patients [2,3,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31]. Table 1 summarizes all diagnosed pediatric patients, while table 2 summarized the adult cases.…”