Monitoring of hematopoietic recovery after autologous stem cell transplantation by analysis of G alpha 16 mRNA and CD34 surface glycoprotein

Pfeilstöcker, Michael; Karlic, H.; Salamon, Julius; Mühlberger, Helmut; Pavlova, Borislava G.; Selim, U; Strobl, Herbert; Pittermann, E.; Heinz, R.

doi:10.1007/s002770050380

Cited by 7 publications

(5 citation statements)

References 14 publications

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“…Onset of G␣16 demonstrated by RT-PCR always preceded an increase of CD34 antigen to a value of Ͼ1% of MNC, irrespective of cytokine administration (Table 1). These data confirm the rise of G␣16 during engraftment after autologous stem cell reinfusion 22 and during stem cell mobilisation. 13 Effects of cytokines are reflected by a specific duration of G␣16 expression after administration of different cytokines (data not shown).…”

Section: Resultssupporting

confidence: 82%

In vivo and in vitro effects of cytokines and the hemoregulatory peptide dimer (pEEDCK)2 (pyroGlu-Glu-Asp-Cys-Lys)2 on Gα16-positive hematopoiesis

et al. 1999

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G proteins play an important role in signal transduction from cytokine receptors to intracellular effectors via different pathways, eg involving tyrosine kinases. In our previous studies, we demonstrated that mRNA expression of the hematopoiesisspecific G protein ␣-subunit G␣16 is a sensitive marker indicating the appearance of early myeloid and lymphoid progenitors. This study was designed to investigate cytokine effects on hematopoiesis in vivo and in vitro as reflected by G␣16 expression and sensitivity to the hemoregulatory peptide (pEEDCK)2 which harbors a structural homology to the effector domain of G␣16. Investigations on blood samples from lymphoma patients undergoing salvage therapy with different cytokine support showed that monitoring of the expression of G␣16 mRNA which appears to play a role in cytokine signalling via tyrosine kinases was a valuable complementation to CD34 screening for analyzing hematopoietic recovery after chemotherapy. We demonstrated that in contrast to CD34 which is only expressed in quiescent cells, G␣16 transcription occurs independently of cell cycle state. In vitro, we could show that G␣16 was also a valuable marker for confirming the immature state of ex vivo expanded blood stem cells from patients. A further part of the study was focused on the response of G␣16 and CD34 expressing cells to the granulocyte-derived hemoregulatory peptide (pyroGlu-Glu-Asp-Cys-Lys)2 = (pEEDCK)2 which harbors a G␣16-homologous sequence motif. Results obtained from in vitro assays which involved estimation of colony outgrowth from CD34-positive cells showed that the effect of (pEEDCK)2 on CD34 cells enhanced the effect of IL-3 or SCF. These data indicate that G␣16 may co-operate with (pEEDCK)2 in triggering the cytokine response of immature hematopoietic cells.

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Section: Resultssupporting

confidence: 82%

In vivo and in vitro effects of cytokines and the hemoregulatory peptide dimer (pEEDCK)2 (pyroGlu-Glu-Asp-Cys-Lys)2 on Gα16-positive hematopoiesis

et al. 1999

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“…Onset of G␣16 demonstrated by RT-PCR always preceded an increase of CD34 antigen to a value of Ͼ1% of MNC, irrespective of cytokine administration (Table 1). These data confirm the rise of G␣16 during Table 1 Correlation of G␣ 16 expression in three lymphoma patients after IEV chemotherapy with or without cytokine rescue with hematopoietic recovery represented by first days of CD34 Ͼ 1% of MNC, WBC Ͼ 1000/mm 3 , Plt Ͼ 50 000/mm 3 22 and during stem cell mobilisation. 13 Effects of cytokines are reflected by a specific duration of G␣16 expression after administration of different cytokines (data not shown).…”

Section: Resultssupporting

confidence: 71%

True

1999

Leukemia

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G proteins play an important role in signal transduction from cytokine receptors to intracellular effectors via different pathways, eg involving tyrosine kinases. In our previous studies, we demonstrated that mRNA expression of the hematopoiesis-specific G protein alpha-subunit G alpha16 is a sensitive marker indicating the appearance of early myeloid and lymphoid progenitors. This study was designed to investigate cytokine effects on hematopoiesis in vivo and in vitro as reflected by G alpha16 expression and sensitivity to the hemoregulatory peptide (pEEDCK)2 which harbors a structural homology to the effector domain of G alpha16. Investigations on blood samples from lymphoma patients undergoing salvage therapy with different cytokine support showed that monitoring of the expression of G alpha16 mRNA which appears to play a role in cytokine signalling via tyrosine kinases was a valuable complementation to CD34 screening for analyzing hematopoietic recovery after chemotherapy. We demonstrated that in contrast to CD34 which is only expressed in quiescent cells, G alpha16 transcription occurs independently of cell cycle state. In vitro, we could show that G alpha16 was also a valuable marker for confirming the immature state of ex vivo expanded blood stem cells from patients. A further part of the study was focused on the response of G alpha16 and CD34 expressing cells to the granulocyte-derived hemoregulatory peptide (pyroGlu-Glu-Asp-Cys-Lys)2 = (pEEDCK)2 which harbors a G alpha16-homologous sequence motif. Results obtained from in vitro assays which involved estimation of colony outgrowth from CD34-positive cells showed that the effect of (pEEDCK)2 on CD34 cells enhanced the effect of IL-3 or SCF. These data indicate that G alpha16 may co-operate with (pEEDCK)2 in triggering the cytokine response of immature hematopoietic cells.

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“…It appears therefore that, besides HSCs, other stem cells including more immature stages like embryonic stem cells and yolk do not express Ga15 (Wilkie et al 1991). In summary, G15 expression cannot be generalized to all stem cells, but overlaps with the CD34 marker for stem and progenitor cell population (Pfeilstöcker et al 1998(Pfeilstöcker et al , 2000. (Wilkie et al (1991)).…”

Section: Hematopoiesismentioning

confidence: 99%

The puzzling uniqueness of the heterotrimeric G15 protein and its potential beyond hematopoiesis

Giannone¹,

Malpeli

Lisi

et al. 2010

Journal of Molecular Endocrinology

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Heterotrimeric G proteins transduce the signals of the largest family of membrane receptors (G protein-coupled receptors, GPCRs) hence triggering the activation of a wide variety of physiological responses. G15 is a G protein characterized by a number of functional peculiarities that make its signaling exceptional: 1) it can couple a variety of Gs-, Gi/o-, and Gq-linked receptors to phospholipase C activation; 2) relatively to other G proteins, it is poorly affected by b-arrestin-dependent desensitization, the general mechanism that regulates GPCR function and 3) at the protein level, its expression is only detected in highly specific cell types (hematopoietic and epithelial cells). G15 a-subunit displays unique structural and biochemical properties, and is phylogenetically the most recent and divergent component of the Gaq/11 subfamily. All these aspects shed a mysterious light on G15 biological role, which remains substantially elusive. Thus, far, G15 signaling has been analyzed in the context of hematopoiesis. Here, we highlight observations supporting the view that G15 functions may extend further beyond the immune system. In addition, we describe puzzling aspects of G15 signaling that offer a novel perspective in the understanding of its physiological role.

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Monitoring of hematopoietic recovery after autologous stem cell transplantation by analysis of G alpha 16 mRNA and CD34 surface glycoprotein

Cited by 7 publications

References 14 publications

In vivo and in vitro effects of cytokines and the hemoregulatory peptide dimer (pEEDCK)2 (pyroGlu-Glu-Asp-Cys-Lys)2 on Gα16-positive hematopoiesis

In vivo and in vitro effects of cytokines and the hemoregulatory peptide dimer (pEEDCK)2 (pyroGlu-Glu-Asp-Cys-Lys)2 on Gα16-positive hematopoiesis

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The puzzling uniqueness of the heterotrimeric G15 protein and its potential beyond hematopoiesis

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