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

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).

• Authors: Richard Ratei, Michael Hummel, Ioannis Anagnostopoulos, Doris Jähne, Renate Arnold, Bernd Dörken, Stephan Mathas, Thomas Benter, Oliver Dudeck, Wolf-Dieter Ludwig, Harald Stein
• Journal: Haematologica (Haematologica) Vol. 95 Issue 9 Pg. 1461-6 (Sep 2010) ISSN: 1592-8721 [Electronic] Italy
• PMID: 20421277 (Publication Type: Case Reports, Journal Article)

Chemical References

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

Topics

• 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, pathology)
• PAX5 Transcription Factor (analysis)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (pathology)