Evidence map›Paper›PMID 27418650›Full record

ArticleHaematologica2016

Stat5 is critical for the development and maintenance of myeloproliferative neoplasm initiated by Nf1 deficiency.

Zohar Sachs, Raha A Been, Krista J DeCoursin, Hanh T Nguyen, Nurul A Mohd Hassan, Klara E Noble-Orcutt, Craig E Eckfeldt, Emily J Pomeroy, Ernesto Diaz-Flores, Jennifer L Geurts and 7 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Haematologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.4field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Review
  3. Pediatric Neoplasms Presenting with Monocytosis.Current hematologic malignancy reports · 2021
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 3 institutions in 1 country.

Zohar SachsDivision of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA sachs038@umn.edu.
Raha A BeenMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA College of Veterinary Medicine and Department of Comparative and Molecular Biosciences, University of Minnesota, St. Paul, MN, USA.
Krista J DeCoursinMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Hanh T NguyenDivision of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Nurul A Mohd HassanMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Klara E Noble-OrcuttDivision of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Craig E EckfeldtDivision of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Emily J PomeroyDivision of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Ernesto Diaz-FloresDepartment of Pediatrics, University of California, San Francisco, CA, USA Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
Jennifer L GeurtsMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Miechaleen D DiersMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Diane E HaszMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Kelly J MorganDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Margaret L MacMillanDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA Blood and Marrow Transplantation Program, University of Minnesota, Minneapolis, MN, USA.
Kevin M ShannonDepartment of Pediatrics, University of California, San Francisco, CA, USA Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
David A LargaespadaMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA Blood and Marrow Transplantation Program, University of Minnesota, Minneapolis, MN, USA.
Stephen M WiesnerMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA Center for Allied Health Programs, University of Minnesota, Minneapolis, MN, USA.
University of Minnesota · USUniversity of Minnesota Medical Center · USUniversity of California, San Francisco · US

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Timothy C. Hallstrom · 1998 to 2026
$100.4M
University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR000114 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R · 2012 to 2015
$35.0M
TRAINING IN HEMOGLOBIN &CELL MEMBRANE RESEARCHT32HL007062 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Jeffrey S. Miller, Gregory M Vercellotti · 1985 to 2026
$10.3M
UNIVERSITY OF MINNESOTA CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE (UMN CTSI)UL1RR033183 · NCRR · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R · 2011 to 2011
$8.9M
MOUSE MODELS OF MYELOID LEUKEMIAU01CA084221 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHANNON, KEVIN M. · 1999 to 2009
$8.7M
University of Minnesota Clinical and Translational Science Institute (UMN CTSI)KL2TR000113 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R · 2012 to 2015
$5.4M
Disordered Regulation of Wnt/beta-catenin Signaling in MPNST Development and MaintenanceR01NS086219 · NINDS · UNIVERSITY OF MINNESOTA · PI LARGAESPADA, DAVID ANDREW, RATNER, NANCY · 2014 to 2018
$2.4M
NCATS NIH HHS KL2 TR000113NCATS NIH HHS UL1 TR000114NCI NIH HHS P30 CA077598NCI NIH HHS U01 CA084221NCRR NIH HHS UL1 RR033183NHLBI NIH HHS T32 HL007062NINDS NIH HHS R01 NS086219
6 · The paper itself

Abstract

Juvenile myelomonocytic leukemia is a rare myeloproliferative neoplasm characterized by hyperactive RAS signaling. Neurofibromin1 (encoded by the NF1 gene) is a negative regulator of RAS activation. Patients with neurofibromatosis type 1 harbor loss-of-function mutations in NF1 and have a 200- to 500-fold increased risk of juvenile myelomonocytic leukemia. Leukemia cells from patients with juvenile myelomonocytic leukemia display hypersensitivity to certain cytokines, such as granulocyte-macrophage colony-stimulating factor. The granulocyte-macrophage colony-stimulating factor receptor utilizes pre-associated JAK2 to initiate signals after ligand binding. JAK2 subsequently activates STAT5, among other downstream effectors. Although STAT5 is gaining recognition as an important mediator of growth factor signaling in myeloid leukemias, the contribution of STAT5 to the development of hyperactive RAS-initiated myeloproliferative disease has not been well described. In this study, we investigated the consequence of STAT5 attenuation via genetic and pharmacological approaches in Nf1-deficient murine models of juvenile myelomonocytic leukemia. We found that homozygous Stat5 deficiency extended the lifespan of Nf1-deficient mice and eliminated the development of myeloproliferative neoplasm associated with Nf1 gene loss. Likewise, we found that JAK inhibition with ruxolitinib attenuated myeloproliferative neoplasm in Nf1-deficient mice. Finally, we found that primary cells from a patient with KRAS-mutant juvenile myelomonocytic leukemia displayed reduced colony formation in response to JAK2 inhibition. Our findings establish a central role for STAT5 activation in the pathogenesis of juvenile myelomonocytic leukemia and suggest that targeting this pathway may be of clinical utility in these patients.

Indexed as

AnimalsDisease Models, AnimalHumansJanus Kinase 2Leukemia, MyeloidLeukemia, Myelomonocytic, JuvenileMiceMyeloproliferative DisordersNeurofibromin 1Proto-Oncogene Proteins p21(ras)Signal TransductionSTAT5 Transcription FactorJAK2 protein, humanJanus Kinase 2Neurofibromin 1Proto-Oncogene Proteins p21(ras)STAT5 Transcription Factor

Identifiers

PMID27418650
PMCPMC5046648
OpenAlexW2461775944

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.