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

Haematologica. 2010 Sep;95(9):1461-6. doi: 10.3324/haematol.2009.021212. Epub 2010 Apr 26.


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,, study-ID:8).

Publication types

  • Case Reports

MeSH terms

  • Cell Transdifferentiation
  • Child
  • Clone Cells / pathology
  • Gene Rearrangement
  • Hematopoiesis*
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Inhibitor of Differentiation Protein 2 / analysis
  • Langerhans Cell Sarcoma / pathology*
  • Leukemia, B-Cell / pathology*
  • Male
  • Neoplasms, Second Primary / etiology
  • Neoplasms, Second Primary / pathology
  • PAX5 Transcription Factor / analysis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*


  • ID2 protein, human
  • Immunoglobulin Heavy Chains
  • Inhibitor of Differentiation Protein 2
  • PAX5 Transcription Factor
  • PAX5 protein, human