Increased expression of the differentiation-defective granulocyte colony-stimulating factor receptor mRNA isoform in acute myelogenous leukemia

White, S. M.; Ball, Edward D.; Ehmann, W. C.; Rao, Abdul S.; Tweardy, David J.

doi:10.1038/sj.leu.2401062

Cited by 30 publications

(25 citation statements)

References 20 publications

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“…In support of this idea, Ehlers et al 25 reported that the expression level of the truncated, differentiationdefective G-CSF receptor isoform IV, known to be overexpressed in some AML patients, 26 was associated with worse outcome in patients who received G-CSF. Our results also have implications for the use of G-CSF "priming" in AML.…”

Section: Discussionmentioning

confidence: 95%

FACS analysis of Stat3/5 signaling reveals sensitivity to G-CSF and IL-6 as a significant prognostic factor in pediatric AML: a Children's Oncology Group report

Redell

Ruiz

Gerbing

et al. 2013

Blood

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Section: Discussionmentioning

confidence: 95%

FACS analysis of Stat3/5 signaling reveals sensitivity to G-CSF and IL-6 as a significant prognostic factor in pediatric AML: a Children's Oncology Group report

Redell

Ruiz

Gerbing

et al. 2013

Blood

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“…The class IV isoform is the product of alternative splicing, which is responsible for tissue-specific variation in the receptor. Myeloid blasts with normal genomic GCSFR DNA also express an increased amount of isoform IV, again resulting from alternative splicing of the mRNA (17). In murine CD34 cells transfected with the isoform IV gene, relatively small increases in the ratio of isoform IV relative to full-length isoform I cause substantial defects in maturation without affecting proliferation (which is controlled by the membraneproximal cytoplasmic domain of the receptor) (19).…”

Section: Discussionmentioning

confidence: 99%

Granulocyte colony-stimulating factor preferentially stimulates proliferation of monosomy 7 cells bearing the isoform IV receptor

Sloand

Yong²,

Ramkissoon

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

107

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Granulocyte colony-stimulating factor (GCSF) administration has been linked to the development of monosomy 7 in severe congenital neutropenia and aplastic anemia. We assessed the effect of pharmacologic doses of GCSF on monosomy 7 cells to determine whether this chromosomal abnormality developed de novo or arose as a result of favored expansion of a preexisting clone. Fluorescence in situ hybridization (FISH) of chromosome 7 was used to identify small populations of aneuploid cells. When bone marrow mononuclear cells from patients with monosomy 7 were cultured with 400 ng͞ml GCSF, all samples showed significant increases in the proportion of monosomy 7 cells. In contrast, bone marrow from karyotypically normal aplastic anemia, myelodysplastic syndrome, or healthy individuals did not show an increase in monosomy 7 cells in culture. In bone marrow CD34 cells of patients with myelodysplastic syndrome and monosomy 7, GCSF receptor (GCSFR) protein was increased. Although no mutation was found in genomic GCSFR DNA, CD34 cells showed increased expression of the GCSFR class IV mRNA isoform, which is defective in signaling cellular differentiation. GCSFR signal transduction via the Jak͞Stat system was abnormal in monosomy 7 CD34 cells, with increased phosphorylated signal transducer and activation of transcription protein, STAT1-P, and increased STAT5-P relative to STAT3-P. Our results suggest that pharmacologic doses of GCSF increase the proportion of preexisting monosomy 7 cells. The abnormal response of monosomy 7 cells to GCSF would be explained by the expansion of undifferentiated monosomy 7 clones expressing the class IV GCSFR, which is defective in signaling cell maturation.hematopoiesis ͉ myelodysplasia ͉ clonal evolution ͉ leukemia ͉ marrow failure

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“…23 It was previously shown that AML cell lines and AML patient samples express increased relative amounts of the class IV isoform G-CSF receptor. 24,25 These data suggest that despite the lack of evidence for an increased risk of relapse associated with G-CSF administration in general, there may be particular AML patient subsets susceptible to this effect. In our study, the number of cases with standard-risk AML was relatively small, so we were able to analyze it separately only in the PB-auto-SCT group.…”

Section: Discussionmentioning

confidence: 98%

Use of G-CSF to hasten neutrophil recovery after auto-SCT for AML is not associated with increased relapse incidence: a report from the Acute Leukemia Working Party of the EBMT

Czerw

Labopin

Gorin

et al. 2014

Bone Marrow Transplant

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Application of G-CSF in AML is controversial as leukemic blasts may express receptors interacting with the cytokine, which may stimulate leukemia growth. We retrospectively analyzed the impact of G-CSF use to accelerate neutrophil recovery after auto-SCT on outcome. Adults with AML in first CR autografted between 1994 and 2010 were included. Nine hundred and seventy two patients were treated with G-CSF after auto-SCT whereas 1121 were not. BM and PB were used as a source of stem cells in 454 (22%) and 1639 (78%) cases, respectively. The incidence of relapse at 5 years in the BM-auto-SCT group was 38% for patients receiving post-transplant G-CSF and 43% for those not treated with G-CSF, P = 0.46. In the PB-auto-SCT cohort, respective probabilities were 48% and 49%, P = 0.49. No impact of the use of G-CSF could be demonstrated with respect to the probability of leukemia-free survival: in the BM-auto-SCT group, 51% for G-CSF(+) and 48% for G-CSF(− ), P = 0.73; in PB-auto-SCT group, 42% for G-CSF(+) and 43% for G-CSF( − ), P = 0.83. Although G-CSF administration significantly shortened the neutropenic phase, no beneficial effect was observed with regard to non-relapse mortality. In patients with AML, the use of G-CSF after auto-SCT is not associated with increased risk of relapse irrespective of the source of stem cells used.Bone Marrow Transplantation (2014) 49, 950-954;

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Increased expression of the differentiation-defective granulocyte colony-stimulating factor receptor mRNA isoform in acute myelogenous leukemia

Cited by 30 publications

References 20 publications

FACS analysis of Stat3/5 signaling reveals sensitivity to G-CSF and IL-6 as a significant prognostic factor in pediatric AML: a Children's Oncology Group report

FACS analysis of Stat3/5 signaling reveals sensitivity to G-CSF and IL-6 as a significant prognostic factor in pediatric AML: a Children's Oncology Group report

Granulocyte colony-stimulating factor preferentially stimulates proliferation of monosomy 7 cells bearing the isoform IV receptor

Use of G-CSF to hasten neutrophil recovery after auto-SCT for AML is not associated with increased relapse incidence: a report from the Acute Leukemia Working Party of the EBMT

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