Abstract
BACKGROUND: Plasmacytoid dendritic cell (DC2) acute leukemia is a recently described hematological malignancy with distinct clinical and phenotypic features. Yet, with fewer than 40 cases studied so far, the cytogenetic profile of this entity is still elusive. Previous studies (Leroux et al, 2002) have revealed recurrent chromosomal aberrations affecting certain genomic targets and the analysis of additional cases is expected to clarify whether these aberrations - alone or in combination - may constitute specific markers for the disease.
METHODS: Seven patients with a well-established diagnosis of DC2AL (based on clinical, morphological and phenotypic features) were included in the study. A conventional cytogenetic analysis (CCA) was performed on unstimulated bone marrow cultures. Additionally, the diagnostic marrow smears were studied with interphase fluorescent in-situ hybridization (FISH), using commercially available probes for 5q31, 6q21, 7q31, 9p21 (p16 gene), 9q34, 11q23 (MLL gene), 12p13 (TEL gene), 13q14, 17p13 (p53 gene) and 21q22 (AML1 gene) regions. In case of any abnormal finding, further study was performed with the use of centromeric or other appropriate arm/chromosome enumeration probe to distinguish between region deletion or overrepresentation and numerical aberrations of the carrier arm/chromosome.
RESULTS: An abnormal karyotype (by either CCA or FISH) was documented in all seven cases studied, with most lesions indicating the loss of genomic material. The most common finding was a rearrangement of the 21q22 region (involving the AML1 gene). Deletions of 6q21, 9q34, 11q23, 12p13 and 13q14, trisomy 12 and trisomy of 13q were detected in only one case each. Interestingly, some aberrations, including the three cases of AML1 rearrangement, were missed on CCA, suggesting a submicroscopic abnormality.
CONCLUSIONS: The study failed to define recurrent chromosomal lesions in DC2AL, other than 21q22 rearrangements. Our results point to a possible pathogenetic role of the AML1 gene. Since AML1 is involved in both myeloid and lymphoid malignancies, it makes a reasonable candidate for leukemogenesis also in the case of DC2AL. Additional investigation at the cytogenetic and molecular level is needed to verify this assumption.
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