Duplication and Amplification of AML1 in a Biphenotypic Acute Leukemia: Mechanism in the Formation of Double Minute Chromosome?.

Amplification of AML1 has been reported in pediatric acute lymphoblastic leukemia (ALL): it occurs mainly older in older children (5 to 14 years-old) as well as in CD10 positive B ALL and a few cases of acute myeloid leukemia. The presence of double minute chromosomes (DMs) may be one of the mechanisms for oncogene up-regulation. It is a rather rare event in hematological malignancies and is generally associated with a poor prognosis. Until now, DMs have been described mainly in AML and involve mainly amplification of c-MYC and MLL.

We report here the case of a 14-year-old boy with CD10 negative biphenotypic acute leukemia (B + M).

Bone marrow cytogenetic analysis revealed a (47, XY) clone with one normal chromosome 21 and two small markers consisting of chromosome 21 material as the sole abnormality. The two markers were consistent with different forms: small acrocentric, small metacentric and appear to be a mixture of those forms until resembling double minute.

Fluorescence in situ hybridization (FISH) was performed using the TEL-AML1 ES probe. Metaphase FISH showed one normal signal, one tandem signal and a third signal with an apparent variable structure. In interphase nuclei, the hybridization showed from 2 to >6 signals without neither tandem duplication nor clustered signals in an area within the interphase nuclei as previously reported in B-ALL.

In our case, we hypothesize that the different forms of the “derivative/deleted” chromosome 21 lead to form DMs containing the AML1 gene. The mechanism seems to be multistep chromosomal rearrangements with formation of an iso-chromosome 21 and deletion of part of chromosome 21.

To our knowledge, it is the first case of biphenotypic AL reported with AML1 amplification and a probable double minute mechanism.