Abstract: Poster Presentations |

HoxB4 Induces Apoptosis in Acute Lymphoblastic Leukemia Reh Cells FREE TO VIEW

Robert J. Pauley, PhD; Yanni Zhuang; Amro Aboukameel; Kamal K. Mubarak, MD*; Larry R. Tait, PhD; Ramzi M. Mohammad, PhD
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Wayne State University, Detroit, MI


Chest. 2004;126(4_MeetingAbstracts):915S. doi:10.1378/chest.126.4_MeetingAbstracts.915S
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PURPOSE:  Pathogenesis of primary pulmonary mucosa-associated lymphoid tumors (MALT) and lymphomas remains unknown, but is thought to involve antigen stimulation leading to immortalization, and then subsequent transformation into a more aggressive phenotype. HoxB4 is a homeobox transcription factor that is known to clonally expand hematopoietic stem cells. We hypothesized that HoxB4 was responsible for transformation and proliferation of lymphoma cells and therefore transfected a pre-B ALL cell line (Reh) with this gene, anticipating increased resistance to chemotherapy. The results were entirely unexpected.

METHODS:  The HoxB4 cDNA was ligated into the mammalian expression vector pLNCX2 and Reh cells were transfected with the plasmid construct using lipofection. Constitutive expression was confirmed by immunocytochemistry.

RESULTS:  The Reh cells transfected with control plasmid began to grow exponentially 4 weeks after transfection. Cells transfected with pLNCX2-HoxB4 declined in number and died. TdT-mediated dUTP nick-end labeling (TUNEL) assay confirmed the presence of DNA disintegration, a hallmark of apoptosis. Immunocytochemistry for caspase-3 confirmed the activation of this enzyme in HoxB4 transfected cells compared to control transfected cells. RT-PCR confirmed the upregulation of FLASH, an activator of the intrinsic apoptosis pathway via caspase-8, compared to controls. Transfection of HoxB4 into other hematopoietic malignant cells has shown that the effect is not limited to just one cell line, but may be present across the entire spectrum of hematological malignancies.

CONCLUSION:  HoxB4 induces apoptosis in hematopoietic malignancies and is known to cause clonal expansion in hematopoietic stem cells.

CLINICAL IMPLICATIONS:  Targeting the HoxB4 gene may have therapeutic benefit in hematological malignancies. Such therapy would most likely enhance host immunity. These effects could be achieved without the side effects of conventional cytotoxic chemotherapy.

DISCLOSURE:  K.K. Mubarak, None.

Wednesday, October 27, 2004

12:30 PM - 2:00 PM




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