Distribution of wheat germ agglutinin binding sites on normal human and guinea pig bone marrow cells: An ultrastructural histochemical study

1979 ◽  
Vol 195 (4) ◽  
pp. 641-657 ◽  
Author(s):  
G. Adolph Ackerman
Keyword(s):  
Bone Marrow ◽  
Guinea Pig ◽  
Binding Sites ◽  
Wheat Germ Agglutinin ◽  
Wheat Germ ◽  
Bone Marrow Cells ◽  
Histochemical Study ◽  
Normal Human ◽  
Marrow Cells

A novel bioaction of PAF: Induction of microbicidal activity in guinea pig bone marrow cells

Lipids ◽  
1988 ◽  
Vol 23 (12) ◽  
pp. 1119-1124 ◽  
Author(s):  
Hidetoshi Hayashi ◽  
Ichiro Kudo ◽  
Toshiyuki Kato ◽  
Ryushi Nozawa ◽  
Shoshichi Nojima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Guinea Pig ◽  
Bone Marrow Cells ◽  
Microbicidal Activity ◽  
Marrow Cells

scholarly journals Differential effects of nitric oxide on erythroid and myeloid colony growth from CD34+ human bone marrow cells

Blood ◽  
1996 ◽  
Vol 87 (3) ◽  
pp. 977-982 ◽  
Author(s):  
PJ Shami ◽  
JB Weinberg
Keyword(s):  
Bone Marrow ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Monocytic Differentiation ◽  
Colony Forming Unit ◽  
Normal Human ◽  
Normal Human Bone Marrow ◽  
Marrow Cells

Nitric oxide (NO) is a reactive molecule with numerous physiologic and pathophysiologic roles affecting the nervous, cardiovascular, and immune systems. In previous work, we have demonstrated that NO inhibits the growth and induces the monocytic differentiation of cells of the HL- 60 cell line. We have also demonstrated that NO inhibits the growth of acute nonlymphocytic leukemia cells freshly isolated from untreated patients and increases monocytic differentiation antigens in some. In the present work, we studied the effect of NO on the growth and differentiation of normal human bone marrow cells in vitro. Mononuclear cells isolated from human bone marrow were cultured in semisolid media and treated with the NO-donating agents sodium nitroprusside (SNP) or S- nitroso-acetyl penicillamine (SNAP) (0.25 to 1 mmol/L). Both agents decreased colony-forming unit-erythroid (CFU-E) and colony-forming unit- granulocyte macrophage (CFU-GM) formation by 34% to 100%. When CD34+ cells were examined, we noted that these cells responded to SNP and SNAP differently than did the mononuclear cells. At a concentration range of 0.25 to 1 mmol/L, SNP inhibited the growth of CFU-E by 30% to 75%. However, at the same concentration range, SNP increased the number of CFU-GM by up to 94%. At concentrations of 0.25 to 1 mmol/L, SNAP inhibited the growth of CFU-E by 33% to 100%. At a concentration of 0.25 mmol/L, SNAP did not affect CFU-GM. At higher concentrations, SNAP inhibited the growth of CFU-GM. Although SNP increased intracellular levels of cGMP in bone marrow cells, increasing cGMP in cells by addition of 8-Br-cGMP (a membrane permeable cGMP analogue) did not reproduce the observed NO effects on bone marrow colonies. These results demonstrate that NO can influence the growth and differentiation of normal human bone marrow cells. NO (generated in the bone marrow microenvironment) may play an important role modulating the growth and differentiation of bone marrow cells in vivo.

scholarly journals Expression of 5′Nucleotidase Activity and Wheat-Germ Agglutinin Binding Sites in Mononuclear Phagocytes From Bone Marrow Cultures

1985 ◽  
Vol 37 (3) ◽  
pp. 263-277 ◽  
Author(s):  
R. de Water ◽  
J.W.M. van der Meer ◽  
J.M. van't Noordende ◽  
J.J.M. Onderwater ◽  
J.S. van de Gevel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Binding Sites ◽  
Wheat Germ Agglutinin ◽  
Wheat Germ ◽  
Mononuclear Phagocytes ◽  
Nucleotidase Activity ◽  
Bone Marrow Cultures ◽  
Marrow Cultures

The rate of sister chromatid exchange in normal human bone marrow cells

1979 ◽  
Vol 50 (2) ◽  
pp. 213-216 ◽  
Author(s):  
R. Becher ◽  
C. G. Schmidt ◽  
Gabriele Theis ◽  
D. K. Hossfeld
Keyword(s):  
Bone Marrow ◽  
Sister Chromatid ◽  
Sister Chromatid Exchange ◽  
Bone Marrow Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Normal Human ◽  
Normal Human Bone Marrow ◽  
Marrow Cells

Induction by platelet activating factor of candidacidal activity in guinea pig bone marrow cells

1988 ◽  
Vol 10 ◽  
pp. 19
Author(s):  
I. Kudo ◽  
H. Hayashi ◽  
T. Kato ◽  
R. Nozawa ◽  
S. Nojima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Guinea Pig ◽  
Bone Marrow Cells ◽  
Platelet Activating Factor ◽  
Marrow Cells

Direct Binding of Grb2 Is Required for Efficient Induction of Myeloproliferative Disease in Mice by ETV6/FLT3.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2903-2903
Author(s):  
Kazuhisa Chonabayashi ◽  
Masakatsu Hishizawa ◽  
Shin Kawamata ◽  
Masashi Matsui ◽  
Tatsuharu Ohno ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tyrosine Kinase ◽  
Binding Sites ◽  
Bone Marrow Cells ◽  
Myeloproliferative Disease ◽  
Juxtamembrane Domain ◽  
Murine Bone Marrow ◽  
Direct Binding ◽  
Marrow Cells

Abstract Abstract 2903 Poster Board II-879 FMS-like tyrosine kinase 3 (FLT3), a class III receptor tyrosine kinase, is one of the most frequently mutated genes in hematological malignancies. The most common mutations of FLT3 are internal tandem duplications (ITDs) within the juxtamembrane domain: these mutations occur in 20% to 30% of patients with AML and are closely associated with a poor prognosis. In a small number of patients with myeloproliferative neoplasms (MPNs), FLT3 has been reported to fuse to ETV6 (TEL) and contribute to leukemogenesis, but the leukemogenic mechanism of ETV6/FLT3 remains unclear. We encountered a case of ETV6/FLT3 fusion in a patient with MPN complicated with T-cell lymphoblastic lymphoma. In this case, both myeloid and lymphoma cells shared the same chromosomal translocation, t(12;13)(p13;q12), and allogeneic hematopoietic stem cell transplantation led to complete remission for 3 years. Full-length ETV6/FLT3 fusion cDNA was cloned from the patient's bone marrow cells. Sequence analysis of the PCR product revealed that, in contrast to the finding of previously reported two cases of ETV6/FLT3-positive MPN, ETV6 exon 6 was fused to FLT3 exon 14 and that the fused portion of ETV6 contained 2 potential Grb2-binding sites (Vu et al., Leukemia 2006; Walz et al., Blood 2007a). The ETV6/FLT3 conferred IL-3-independent growth to Ba/F3 and 32Dcl3 cells. Using a dominant negative approach, we showed that both STAT5 and Ras played important roles in ETV6/FLT3-mediated transformation of the hematopoietic cell lines. To investigate the role of the ETV6/FLT3 fusion protein in vivo, we used a murine bone marrow transplant model. Retroviral transduction of the ETV6/FLT3 into primary murine bone marrow cells resulted in a CML-like myeloproliferative disease (MPD) with complete penetrance in the transplanted mice. The disease progressed to cause death at a median of 18 days after transplantation (n = 16). The transplanted mice developed severe leukocytosis (159 × 103 /μl to 417 × 103 /μl), splenomegaly, and extensive infiltration of myeloid cells in the bone marrow, spleen, liver, and peripheral blood. ETV6/FLT3-induced MPD was oligoclonal and only 2 of the 9 secondary transplant recipients developed similar MPD when 5 × 106 spleen cells from 3 independent diseased mice were used as donors. We assayed the mutant forms of the ETV6/FLT3 to test their ability to transform hematopoietic cells. Induction of MPD required the oligomerization domain of ETV6 and the tyrosine kinase activity of FLT3. Mice that received the double tyrosine-to-phenylalanine mutant of ETV6/FLT3 at sites 589 and 591 (Y589/591F) in the juxtamembrane domain of FLT3, which are critical for FLT3-ITD-induced MPD, also developed a similar MPD phenotype. Unlike FLT3-ITDs, Y589/591F mutation did not abrogate STAT5 activation in Ba/F3 and 32Dcl3 cells transformed by ETV6/FLT3. A recent study has shown that direct binding of Grb2 to tyrosine 768, 955, and 969 of FLT3 is important for FLT3-ITD-mediated proliferation and survival of hematopoietic cells. Tyrosine 314 in exon 5 of ETV6 has also been reported as the principal Grb2-binding site that contributes to leukemogenesis via oncogenic ETV6 fusion proteins such as ETV6/ABL. Thus, we next investigated the role of Grb2 binding in ETV6/FLT3-mediated leukemogenesis. Using coimmunoprecipitation assays, we demonstrated that Grb2 also binds to the tyrosine 314 and 354 of ETV6 of the ETV6/FLT3, in addition to the tyrosine 768, 955, and 969 of FLT3. Both ETV6/FLT3-Y314/354F and ETV6/FLT3-Y768/955/969F retained their interaction with Grb2 and induced rapidly fatal MPD when they were transduced into primary murine bone marrow cells. On the other hand, the ETV6/FLT3 mutant at all the binding sites of Grb2 (Y314/354/768/955/969F) significantly attenuated MPD development in mice. Simultaneous mutation of these 5 tyrosine residues completely abolished the binding of Grb2 and resulted in a marked decrease in the binding and phosphorylation of Gab2 and impaired activation of STAT5 and Akt in Ba/F3 cells. These results indicate that tyrosine 589 and 591 of FLT3 are dispensable for the ETV6/FLT3-induced MPD phenotype, and suggest that both ETV6 and FLT3 portions contribute to the ETV6/FLT3-mediated leukemogenesis by binding directly to Grb2. Our observations provide deep insights into the oncogenic signaling induced by active FLT3 mutants as well as provide a potential target for therapies. Disclosures: No relevant conflicts of interest to declare.

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