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Thirty cases of acute myeloid leukaemia (AML) with MYST histone acetyltransferase 3 (MYST3) rearrangement were collected in a retrospective study from 14 centres in France and Belgium. The mean age at diagnosis was 59.4 years and 67% of the patients were females. Most cases (77%) were secondary to solid cancer (57%), haematological malignancy (35%) or both (8%), and appeared 25 months after the primary disease. Clinically, cutaneous localization and disseminated intravascular coagulation were present in 30 and 40% of the cases, respectively. AMLs were myelomonocytic (7%) or monocytic (93%), with erythrophagocytosis (75%) and cytoplasmic vacuoles (75%). Immunophenotype showed no particularity compared with monocytic leukaemia without MYST3 abnormality. Twenty-eight cases carried t(8;16)(p11;p13) with MYST3-CREBBP fusion, one case carried a variant t(8;22)(p11;q13) and one case carried a t(8;19)(p11;q13). Type I (MYST3 exon 16-CREBBP exon 3) was the most frequent MYST3-CREBBP fusion transcript (65%). MYST3 rearrangement was associated with a poor prognosis, as 50% of patients deceased during the first 10 months. All those particular clinical, cytologic, cytogenetic, molecular and prognostic characteristics of AML with MYST3 rearrangement may have allowed an individualization into the World Health Organization classification.Leukemia (2008) 22, 1567–1575; doi:10.1038/leu.2008.128; published online 5 June 2008 [ABSTRACT FROM AUTHOR]

Cytogenetic studies of acute myeloid leukaemias reveal non-random chromosomal abnormalities in 50–70% of karyotypes. Some are correlated with morphological and immunological parameters and constitute a prognostic factor independent of the other factors of risk: favourable for acute leukaemias myeloid with translocations t(8 ;21), t(15 ;17) and inversion or translocation of the chromosome 16, inv(16)/t(16 ;16), poor with deletion of the long arm of chromosome 5 del(5q), rearrangement of the 11q23 region and complex karyotypes. The distribution of the anomalies depends on the age: 11q23 and t(8;21) more frequent for the child, del(5q) and complex anomalies more frequent for the adult.The karyotypes are essential for the diagnosis, the follow-up of the patients and the evaluation of the relapse. It plays a fundamental part in the detection of new genes and their partners implied in the leucemogenese. The knowledge of their function is essential to open new therapeutic ways. [Copyright &y& Elsevier]

The MLL gene, located at 11q23, is frequently rearranged in acute leukaemia as either chimaeric fusion genes or partial tandem duplications. We report a series of 12 acute leukaemia cases with apparent amplification of the MLL gene ascertained using fluorescence in situ hybridisation (FISH). Seven cases showed intrachromosomal amplification of MLL, four cases showed extrachromosomal amplification as double minute chromosomes (dmin) and one case had separate subclones with dmin and homogenously staining region (hsr). Southern blot analysis of the MLL gene showed MLL gene rearrangement in three of the 10 successful cases. These cases do not naturally fall into either of the two recognised categories of MLL rearrangement and may represent a third variety of MLL gene abnormalities. [ABSTRACT FROM AUTHOR]

Therapy-related leukemia associated with chemotherapy, particularly alkylating agents and topoisomerase II inhibitors, are being reported with increasing frequency in the literature mainly after breast cancer. We also observed an increasing number of such leukemias in the data base of the specialized registry of hematological malignancies of the Côte d'Or department. Between 1980 and 1998, 156 AML and RAEB-t were registered in women in Côte d'Or. Among them, 12 occurred in women with breast cancer history (7.7%). Analysis by period of time shows a significant increase in the proportion of therapy-related leukemia secondary to breast cancer (P < 0.02). Chemotherapy including topoisomerase II inhibitors was used in 10 cases in which mitoxantrone was used in eight cases. In these eight cases, leukemia had clinical and biological characteristics usually described with topoisomerase II inhibitors but 44% were promyelocytic sub-type with the t(15;17) specific karyotypic abnormality. These data on a well-defined population demonstrate the increased proportion of therapy-related leukemia secondary to breast cancer, probably due to the use of mitoxantrone. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented that discusses the analyses of TET2 mutations in post-myeloproliferative neoplasm acute myeloid leukemias.