Intrinsic inhibition of transcription factor E2A by HLH proteins ABF-1 and Id2 mediates reprogramming of neoplastic B cells in Hodgkin lymphoma

Hodgkin lymphoma (HL) is characterized by the malignant growth of the so-called Hodgkin/Reed-Sternberg (HRS) cells in the  lymph system. These lymphoma cells originate from B cells but display a non-B cell phenotype. Now, Stephan Mathas and Martin Janz (laboratory of Professor Bernd Dörken) and collaborators have discovered a molecular mechanism that results in the reprogramming of the neoplastic B cells in HL and, hence, offers an explanation for the among human lymphomas unique HL phenotype (Nature Immunology. 2006  7:207-215).

The researchers used HRS cells to demonstrate that human lymphoid cells also undergo lineage changes. Specifically, Drs. Mathas and Janz showed that the helix-loop-helix (HLH) proteins ABF-1 and Id2 inhibit the HLH transcription factor E2A, a central regulator of B cell development. As a result, expression of genes specific to B cells was lost and expression of B lineage-inappropriate genes was upregulated. These new findings show that mature human lymphoid cells are plastic, thereby challenging the previous rigid view of cellular differentiation. What remains to be clarified are the exact molecular mechanisms that regulate Id2 and ABF-1 in HRS cells. These insights into the biology of HL contribute to the understanding of the differentiation process of normal and malignant B lymphoid cells


Pamela Cohen
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