Expression of HOXC4, HOXC5, and HOXC6 in human lymphoid cell lines, leukemias, and benign and malignant lymphoid tissue

Abstract

Besides their regulatory role in embryogenesis, homeobox (HOX) genes are expressed in a specific manner in hematopoietic cell lineages, implying a role in the molecular regulation of hematopoiesis. Some HOX C cluster genes are found to be expressed in lymphoid cells of mice and humans. Their function and expression in normal hematopoiesis are still largely unknown. We have studied the mRNA expression of HOXC4, HOXC5, and HOXC6 in several stages of lymphocyte maturation by reverse transcriptase-polymerase chain reaction (RT-PCR) and RNA in situ hybridization (RISH). We examined CD34+/CD38low and CD34+/CD38high cells obtained from normal donor bone marrow (BM), a panel of 19 lymphoid cell lines, several types of leukemias and non-Hodgkin's lymphomas (NHL), and lymphocytes isolated from tonsillar tissue and peripheral blood (PB). HOXC4 and HOXC6 were found to be expressed during maturation in B- and T-lymphoid cells. The expression of each gene was found to be initiated at different cell maturation stages. HOXC4 transcripts were present in CD34+/CD38low cells, which are thought to comprise stem cells and noncommitted progenitor cells, and in subsequent stages to terminally maturated lymphoid cells. HOXC6 expression is initiated in equivalents of prothymocyte and pre-pre-B cell stage and remains present in mature cells. However, HOXC5 is only expressed in neoplastic cell lines and in neoplastic cells of NHL, but not in CD34+ BM cells, nor in resting or activated lymphoid cells isolated from tonsil, PB, or in leukemia cells. In cell lines, weak expression of HOXC5 is initiated in equivalents of pre-B cell and common thymocyte stage and is continuously expressed in mature cell lines. Semi-quantitative RT-PCR showed that expression levels of HOXC5 were much lower than those of HOXC4 and HOXC6; furthermore an increase of expression of HOXC4, HOXC5, and HOXC6 during lymphoid cell differentiation was demonstrated. Thus, mainly mature lymphoid cell lines and neoplastic cells of NHL do express HOXC5, in contrast to the lack of expression in normal lymphoid cells and leukemias. These findings suggest involvement of HOXC5 in lymphomagenesis.

HOXC6 in the prognosis of prostate cancer

“…It is reported that HOXC6 participates in milk production and mammary gland development [15,16]. Moreover, aberrant expression of HOXC6 has been reported in various cancers, such as head and neck squamous cell carcinoma, gastrointestinal cancer, breast cancer, leukemia and osteosarcoma [15,[17][18][19][20]. In earlier researches, HOXC6 showed raising tendency in PCa and was involved in the cancer development [21,22].…”

In vivo transcription of the Epstein–Barr virus (EBV) BamHI-A region without associated in vivo BARF0 protein expression in multiple EBV-associated disorders

“…RT-PCR primers and probes are listed in Table 1. As a positive and RNA quality control, RT-PCR for snRNP U1A, a low-abundance RNA transcript, was performed on all samples as described previously (Bijl et al, 1995). All samples were analysed by multi-primed RT-PCR for mRNA encoding EBNA1 (driven by the Cp, Wp or Qp promoters), LMP1, LMP2A, LMP2B and the BARTs (A3/A4), according to Brink et al (1997a).…”

Human hematopoietic lineage commitment

“…Overexpression of HOXC4 in CD34 + cells has been shown to dramatically increase the proliferation of LTC‐IC as well as myeloid and erythroid CFCs (72). HOXC4 transcripts have been detected in CD34 + CD38 + progenitors and in terminally differentiated T and B cells (73) but not in mature granulocytes or monocytes (74). Expression of HOXC6 has been detected in mature T lineage cells, but not in CD34 + progenitors, suggesting that it functions later in lymphoid differentiation.…”