Common clonal origin of an acute B-lymphoblastic leukemia and a Langerhans' cell sarcoma: evidence for hematopoietic plasticity
Open Access
- 26 April 2010
- journal article
- research article
- Published by Ferrata Storti Foundation (Haematologica) in Haematologica
- Vol. 95 (9), 1461-1466
- https://doi.org/10.3324/haematol.2009.021212
Abstract
Background The hierarchical organization of hematopoiesis with unidirectional lineage determination has become a questionable tenet in view of the experimental evidence of reprogramming and transdifferentiation of lineage-determined cells. Clinical examples of hematopoietic lineage plasticity are rare. Here we report on a patient who presented with an acute B-lymphoblastic leukemia and developed a Langerhans’ cell sarcoma 9 years later. We provide evidence that the second neoplasm is the result of transdifferentiation. Design and Methods B-cell acute lymphoblastic leukemia was diagnosed in an 11-year old boy in 1996. Treatment according to the ALL-BFM-1995 protocol resulted in a complete remission. Nine years later, in 2005, Langerhans’ cell sarcoma was diagnosed in a supraclavicular lymph node. Despite treatment with different chemotherapy protocols the patient had progressive disease. Finally, he received an allogeneic peripheral blood stem cell transplant and achieved a continuous remission. Molecular studies of IGH- and TCRG-gene rearrangements were performed with DNA from the Langerhans’ cell sarcoma and the cryopreserved cells from the acute B-lymphoblastic leukemia. The expression of PAX5 and ID2 was analyzed with real-time reverse transcriptase polymerase chain reaction. Results Identical IGH-rearrangements were demonstrated in the acute B-lymphoblastic leukemia and the Langerhans’ cell sarcoma. The key factors required for B-cell and dendritic cell development, PAX5 and ID2, were differentially expressed, with a strong PAX5 signal in the acute B-lymphoblastic leukemia and only a weak expression in the Langerhans’ cell sarcoma, whereas ID2 showed an opposite pattern. Conclusions The identical IGH-rearrangement in both neoplasms indicates transdifferentiation of the acute B-lymphoblastic leukemia into a Langerhans’ cell sarcoma. Loss of PAX5 and the acquisition of ID2 suggest that these key factors are involved in the transdifferentiation from a B-cell phenotype into a Langerhans’/dendritic cell phenotype. (Clinical trial registration at: Deutsches KrebsStudienRegister, http://www.studien.de, study-ID:8)This publication has 21 references indexed in Scilit:
- B lymphocytes: how they develop and functionBlood, 2008
- Clonally related follicular lymphomas and histiocytic/dendritic cell sarcomas: evidence for transdifferentiation of the follicular lymphoma cloneBlood, 2008
- Pax5: the guardian of B cell identity and functionNature Immunology, 2007
- Differential involvement of PU.1 and Id2 downstream of TGF-β1 during Langerhans-cell commitmentBlood, 2006
- Flk2+ myeloid progenitors are the main source of Langerhans cellsBlood, 2006
- Intrinsic inhibition of transcription factor E2A by HLH proteins ABF-1 and Id2 mediates reprogramming of neoplastic B cells in Hodgkin lymphomaNature Immunology, 2005
- Transcriptional profiling identifies Id2 function in dendritic cell developmentNature Immunology, 2003
- Long-term results of four consecutive trials in childhood ALL performed by the ALL-BFM study group from 1981 to 1995Leukemia, 2000
- IDENTIFICATION OF A NOVEL CELL TYPE IN PERIPHERAL LYMPHOID ORGANS OF MICEThe Journal of Experimental Medicine, 1973
- Ueber die Nerven der menschlichen HautVirchows Archiv, 1868