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Acute myeloid leukemia in a patient with ataxia-telangiectasia: a case report and review of the literature

Leukemia volume 15, pages 1668–1670 (2001)Cite this article

Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by cerebral degeneration, immunodeficiency, cancer predisposition, radiation sensitivity and cell cycle abnormalities. This unique phenotype is due to the mutated gene ATM that is located on chromosome 11q22–231 and the carriers’ frequency of AT locus mutations is about 1.5–3% of the general population.2 Compared with non-carriers, the heterozygotes for ATM mutations died 7 to 8 years earlier, mainly due to cancer and heart strokes,3 while homozygotes have an increased risk for developing malignancies, especially of lymphoid origin,4 like acute lymphoblastic leukemia (ALL), lymphomas or prolymphocytic leukemia (PLL). Even if B cell tumors are often in AT patients, there is a four- to five-fold increased frequency of T cell tumors compared with that of B cell origin in these patients.5 Abnormal expression of ATM protein is a frequent finding in patients with B cell chronic lymphocytic leukemia (B-CLL) and approximately 14% of these patients carry deletions of the long arm of chromosome 11 at 11q22–23 resulted in a significant shorter survival time.6 ATM is implicated in cell cycle control and DNA repair whose inactivation is considered as a major event in T cell PLL, while loss of heterozygosity of the ATM gene and protein deficiency have been described in adult ALL, as well as in indolent or aggressive lymphomas.7 However, even if the presence of lymphoid disorders has been demonstrated in AT patients, there is a total absence of myeloid tumors. According to our knowledge, there is no such a case in the literature. We describe a female with typical AT who initially developed a myelodysplastic syndrome (MDS) that progressed to acute myeloid leukemia (AML).

The possible role of the ATM gene in cancer predisposition in the general population made it a target for screening in different malignancies. Loss of heterozygosity at the ATM gene and ATM protein deficiency have been described in ALL, B-CLL, T-PLL and NHL,4 possibly representing major determinants for the prognosis of these disorders. As ATM seems to be required for the normal rearrangement of the T cell receptor alpha/delta locus, it might be reasonable to speculate that this mechanism is associated with the development of lymphoid origin tumors in individuals with ATM mutations. However, despite the demonstrated relationship between ATM and lymphoid malignancies, the presence of myeloid tumors in patients with AT or in carriers of ATM mutation had not been described. The female presented here had a typical AT and developed an MDS of RAEB subtype, with a deletion of the region q22;23 of chromosome 11, which progressed to AML (M2) without any other cytogenetic abnormalities. This was confirmed with a second cytogenetic analysis. Although no translocation involving chromosomes 14 (14q11-TcRα/δ) or 7 (7q35-TcRβ and 7p14-TcRγ) was detected in our patient, PCR analysis was performed and confirmed no rearrangement of TcR genes. Also at the genetic level of B-lymphocytes no evidence for clonality was shown by PCR analysis.

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  1. First Department of Internal Medicine, University of Athens School of Medicine, Laikon General Hospital, Athens, Greece

    N Viniou, E Terpos, J Rombos, G Vaiopoulos, K Nodaros, K Stamatopoulos, J Meletis & X Yataganas

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Viniou, N., Terpos, E., Rombos, J. et al. Acute myeloid leukemia in a patient with ataxia-telangiectasia: a case report and review of the literature. Leukemia 15, 1668–1670 (2001). https://doi.org/10.1038/sj.leu.2402210

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