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Occurrence of identical NOTCH1 mutation in non-twinned sisters with T-cell acute lymphoblastic leukemia

Leukemia volume 25, pages 1368–1370 (2011)Cite this article

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Sporadic cases of hematological malignancies in children or young adults or embryonic tumors in sibling pairs have raised speculation that genetic susceptibility factors may be associated with these diseases.1, 2 Recent genome-wide association studies in childhood acute lymphoblastic leukemia (ALL) have identified inherited gene variants associated with increased risk of disease.3 The excess of familial cancer occurrence may also be attributable to the fact that sibs share common environmental exposures, but studies to address this aspect are scarce.2

The acquired genetic aberrations in T-ALL include chromosomal translocations (frequently involving TCR) as well as gene rearrangements and mutations resulting in abnormal expression of genes such as NOTCH1, TAL1, HOX11, HOX11L2, LMO1 and LMO2.4 Acquired NOTCH1 mutations are present in ∼50% of T-ALL cases.5 NOTCH1 signaling is crucial for several steps in T-cell differentiation and also acts on proliferation and survival of these cells. Therefore, the mutational activation of this gene is an important factor in T-ALL pathogenesis.4 In one case of T-ALL, NOTCH1 mutation was pre-natal and preceded SIL–TAL fusion,6 suggesting that it might, at least in some cases, be an early and initiating genetic lesion. Animal models reveal that NOTCH1 mutations can initiate T-cell leukemia7 or arise as secondary, genetic lesions.8

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Acknowledgements

MSPO has been supported by grants from INCT para Controle do Cancer, CNPq 573806/2008-0 and FAPERJ E26/170.026/2008. MBM is supported by the CAPES Foundation. ME is supported by INCA/MS. AMF and MG are supported by a programme grant from Leukaemia Lymphoma Research (London).

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Authors and Affiliations

  1. Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil

    M B Mansur, M Emerenciano & M S Pombo-de-Oliveira

  2. Section of Haemato-Oncology, The Institute of Cancer Research, Sutton, Surrey, UK

    A M Ford, F W van Delft, D Gonzalez & M Greaves

  3. Laboratory of Cellular and Molecular Hematology, Hospital do Câncer, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil

    R C Maia

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  1. M B Mansur
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  2. A M Ford
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  3. F W van Delft
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  5. M Emerenciano
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  6. R C Maia
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  8. M S Pombo-de-Oliveira
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Correspondence to M S Pombo-de-Oliveira.

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Mansur, M., Ford, A., van Delft, F. et al. Occurrence of identical NOTCH1 mutation in non-twinned sisters with T-cell acute lymphoblastic leukemia. Leukemia 25, 1368–1370 (2011). https://doi.org/10.1038/leu.2011.96

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