HOXC4, HOXC5, AND HOXC6 EXPRESSION IN PRIMARY CUTANEOUS LYMPHOID LESIONS - HIGH EXPRESSION OF HOXC5 IN ANAPLASTIC LARGE-CELL LYMPHOMAS

Homeobox (HOX) genes are involved in the lineage specific differentiat ion of bone marrow stem cells. Recently, we reported a largely similar expression pattern of HOXC4 and HOXC6 in normal and neoplastic cells of the lymphoid lineage. In contrast, HOXC5 was specifically expressed in a subset of B-cell non-Hodgkin's lymphomas (B-NHL) but not in norm al lymphocytes or lymphoid leukemias. This might suggest a role for HO XC5 in the pathogenesis of these lymphomas. In the present study the e xpression of HOXC4, HOXC5, and HOXC6 in primary cutaneous lymphomas wa s investigated. Using RNA in situ hybridization (RISH) and semiquantit ative reverse transcriptase polymerase chain reaction (RT-PCR), we fou nd strong expression of HOXC4 and HOXC6 in all, except one, primary cu taneous lymphomas and all reactive cutaneous lymphoid infiltrates. Int erestingly, a strong expression of HOXC5 in primary anaplastic CD30(+) large T-cell lymphomas was found, RISH was consistently negative for HOXC5 in all other types of primary cutaneous B- and T-cell lymphomas. However, by semiquantitative RT-PCR these lymphomas showed a weak exp ression of HOXC5 mRNA. Therefore, we concluded that these lymphomas ex press low constitutive levels of HOXC5 mRNA, Furthermore, HOXC5 expres sion was consistently absent in reactive cutaneous lymphoid infiltrate s, hyperplastic tonsils and lymph nodes, and peripheral blood lymphocy tes either unstimulated or stimulated by a cocktail of CD3 and CD28 an tibodies. As a strong expression of HOXC5 in primary cutaneous lymphom as was observed only in anaplastic large T-cell lymphomas and reactive control tissues lacked HOXC5 expression, these data strongly support a role for HOXC5 in the genesis of anaplastic large-T-cell lymphomas.