Growth Factor Receptors in Hematopoietic Stem Cells: EPH Family Expression in CD34+ and CD133+ Cell Populations from Mobilized Peripheral Blood

Abstract

Cell-surface antigen expression of hematopoietic stem cells has a crucial role in characterizing cell subpopulation with distinct functional properties. The Eph receptors are the largest receptor tyrosine kinase family being involved in processes like vascular remodelling during development and physiological and pathological angiogenesis. Some EphlEphrin members are expressed in hematopoietic cells. The ability to isolate purified cell populations co-expressing CD34 and CD133 antigens as most commonly used markers for identification of hematopoietic progenitors has provided the opportunity to identify their surfacereceptor profile, As positively expressed CD34 and CD133 cells take place not only in hematopoietic but also in endothelial differentiation, we aimed to define the EphlEphrin characteristic ofthese cells and relate these findings to new therapy strategies. Positive selections of CD34 and CD133 cells from PBPC in lymphoma patients were performed using magnetic beads and AutoMACS (Miltenyi Biotec) device. The purity of isolated cells was tested by flow cytometry. Immunocytochemistry was used to assess the EphlEphrin expression profile of positively selected samples. Our study revealed that all samples (10 from CD34+ and 8 from CD133+ cells) expressed one or more of EphlEphrin antigens in different proportions. AU CD34 + cell samples, and 6 of 8 in the CD133+ cell fraction were strongly immunoreactive for EphA2. EphB2 was strongly expressed in all CD133+ cases, but 50% of the CD34 positive group lacked or weakly expressed this receptor. EphB4 was negative in 9 of 10 CD34+ cases and in all CD133 +cells. Thus, we have shown the surface marker profile of positively selected CD34 and CD133 cells in leukapheresis samples from lymphoma patients with regard to EphlEphrin receptors and discussed their biological clinical potential.

Overcoming the Response Plateau in Multiple Myeloma: A Novel Bortezomib-Based Strategy for Secondary Induction and High-Yield CD34+ Stem Cell Mobilization

“…Ephrin receptor signaling is known to play a role in cell migration (30)and can be differentially expressed in mobilized hematopoietic stem cells (31). In order to determine if differential gene expression in these highest-ranked pathways could account for enhanced bortezomib-induced mobilization of CD34+ cells, the list of genes was filtered for those with known functional roles in cell migration.…”

The relationship between Bcl-2 gene expression and learning & memory impairment in chronic aluminum-exposed rats

“…Bcl-2 over-expression inhibits neuronal apoptosis induced by diverse causes, including ischemia, anoxia and hyperthermia Passam et al, 2006). Under normal conditions, Bcl-2 regulates cellular apopto-sis, in opposition to the pro-apototic cellular protein Bax (Cadoni et al, 2007;Deepak et aL, 2007), thereby preserving cellular function (Lanzilli et al, 2006;Lazarova et al, 2006;Staibano et aL, 2006). Under normal conditions, Bcl-2 regulates cellular apopto-sis, in opposition to the pro-apototic cellular protein Bax (Cadoni et al, 2007;Deepak et aL, 2007), thereby preserving cellular function (Lanzilli et al, 2006;Lazarova et al, 2006;Staibano et aL, 2006).…”

Immunotherapy of cancer: Some up-to-date approaches

“…This has prompted the development of various vaccines [1] to target defined or undefined melanoma antigens. [2,3,4,5,6,7,8], but there is limited evidence of clinical effect With regard to non-specific immunostimulation, high-dose interleukin-2 (IL-2) has been shown to induce complete remission in about 16% of melanoma patients, but is associated with considerable adverse effects. IL-2, Interferon-alpha (INF-alpha) and other cytokines are also investigated in combination with conventional chemotherapy.…”

“…Several differentiation antigens are extensively used in cancer vaccines, including prostatespecific antigen (PSA) and the melanoma antigens Melan a/Mart-1, gp100 and tyrosinase [6,7,8].…”