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Common clonal origin of an acute B lymphoblastic leukemia and a Langerhans' cell sarcoma: evidence for hematopoietic plasticity

Item Type:Article
Title:Common clonal origin of an acute B lymphoblastic leukemia and a Langerhans' cell sarcoma: evidence for hematopoietic plasticity
Creators Name:Ratei, R. and Hummel, M. and Anagnostopoulos, I. and Jaehne, D. and Arnold, R. and Doerken, B. and Mathas, S. and Thomas, B. and Dudeck, O. and Ludwig, W.D. and Stein, H.
Abstract:Background. The hierarchical organization of the hematopoiesis with unidirectional lineage determination has become a questionable tenet in view of the experimental evidence for 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 (B-ALL) and developed a Langerhans cell sarcoma (LCS) nine years later. We provide evidence that the second neoplasm is the result of a transdifferentiation. Design and Methods. B-ALL 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, LCS 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 transplantation and achieved a continuous remission. Molecular studies of IgH- and TCRgamma- gene rearrangements were performed with DNA from the LCS and the cryopreserved cells from the B-ALL. The expression of PAX5 and Id2 was analyzed with real-time RT-PCR. Results. Identical IgH-rearrangements in the B-ALL and the LCS were demonstrated. The key factors required for B-cell and dendritic cell development PAX5 and Id2 were differentially expressed, with a strong PAX5 signal in the B-ALL and only a weak expression in the LCS, whereas Id2 showed an opposite pattern. Conclusions. The identical IgH-rearrangement in both neoplasms indicates a transdifferentiation of the B-ALL into a LCS. 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.
Keywords:Hematopoiesis, Stem Cell Plasticity, Pediatric Acute Lymphoblastic Leukemia
Publisher:Ferrata Storti Foundation
Page Range:1461-1466
Date:September 2010
Official Publication:https://doi.org/10.3324/haematol.2009.021212
PubMed:View item in PubMed

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