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PDGFRA rearrangement leading to hyper-eosinophilia, T-lymphoblastic lymphoma, myeloproliferative neoplasm and precursor B-cell acute lymphoblastic leukemia

Leukemia volume 25, pages 371–375 (2011)Cite this article

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The recent World Health Organization (WHO) classification clearly defined a new entity, named ‘myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB and FGFR1’, as a category of three rare specific but related disease groups.1 They are characterized by the formation of a fusion gene encoding an aberrant tyrosine kinase and almost always associated with peripheral blood eosinophilia.1 Myeloid and lymphoid neoplasms with PDGFRA rearrangement are unique disease entities mostly characterized by the formation of a fusion gene FIP1L1–PDGFRA, as a result of a cryptic deletion at chromosome 4q12.1, 2 The disease presents generally as chronic eosinophilic leukemia but can also present as acute myeloid leukemia, T-lymphoblastic lymphoma or both simultaneously. Although the hematopoietic stem cell has been postulated as a possible cellular origin of the disease, clinical manifestations are apparently limited only to the myeloid and T-cell lineages both in chronic phase and in acute leukemic transformation.1, 2 In this study we present an extremely rare case, in which a single genetic abnormality (PDGFRA rearrangement) led to multiple morphologically and immunophenotypically distinct diseases, including T-lymphoblastic lymphoma, a myeloproliferative neoplasm with eosinophilia and abnormal mastocytosis, and a precursor B-cell acute lymphoblastic leukemia, thus involving all three major hematopoietic lineages, that is, myeloid, T-cell and B-cell in the same patient, truly representing a ‘pluripotent hematopoietic stem cell disorder.’

This is a very unique and extremely interesting case. The patient initially had typical presentations with both bone marrow chronic myeloproliferative disorders with eosinophilia and atypical accumulation of neoplastic mast cells and T-lymphoblastic lymphoma in the lymph node simultaneously. Florescence in situ hybridization analysis clearly demonstrated that both myeloid and T-lymphoid lesions shared the same chromosomal abnormality with FIP1L1–PDGFRA translocation, which has well been recognized by the recent WHO classification as a new disease entity and has been reported in the literature.1, 2 Acute phase of the disease may occur, usually myeloid or T-lymphoblastic, according to the WHO classification.1, 2 However, the current patient developed a rather characteristic precursor B-cell acute lymphoblastic leukemia during the course of treatment, a little more than 1 year after his initial diagnosis. Cytogenetic and molecular analysis unequivocally demonstrated the presence of FIP1L1–PDGFRA translocation in the T-lymphoblastic lymphoma and chronic myeloproliferative neoplasm, presumably including eosinophils and mast cells and the later precursor B-cell acute lymphoblastic leukemia. The results clearly show that the three distinctive disorders shared a common fundamental molecular genetic abnormality and indicate that they may undergo a common process in pathogenesis. Additional chromosomal abnormalities identified in precursor B-cell acute lymphoblastic leukemia indicated clonal evolution of the disease, whereas the exact pathogenesis and mechanism of multilineage involvement and manifestation of the disease bearing a single known molecular genetic abnormality in FLP1L1–PDGFRA translocation, however, remains to be elucidated. To the best of our knowledge, PDGFRA rearrangement cases with evolution to precursor B-cell acute lymphoblastic leukemia have not been recognized by the new 2008 WHO Classification and have not been described in the literature.1, 2

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Acknowledgements

We gratefully thank the excellent technical support from Nancy Y Hsn in cytogenetic co-facilities in the City of Hope National Medical Center.

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  1. Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA

    Q Huang, P Chu, K K Gaal, K L Chang & L M Weiss

  2. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA

    D S Snyder

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  1. Q Huang
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Correspondence to Q Huang.

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Huang, Q., Snyder, D., Chu, P. et al. PDGFRA rearrangement leading to hyper-eosinophilia, T-lymphoblastic lymphoma, myeloproliferative neoplasm and precursor B-cell acute lymphoblastic leukemia. Leukemia 25, 371–375 (2011). https://doi.org/10.1038/leu.2010.272

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