Helmholtz Gemeinschaft


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., Hummel, M., Anagnostopoulos, I., Jaehne, D., Arnold, R., Doerken, B., Mathas, S., Thomas, B., Dudeck, O., 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

Repository Staff Only: item control page

Open Access
MDC Library