Evidence map›Paper›PMID 22685175›Full record

ArticleBlood2012

Aberrant STAT5 and PI3K/mTOR pathway signaling occurs in human CRLF2-rearranged B-precursor acute lymphoblastic leukemia.

Sarah K Tasian, Michelle Y Doral, Michael J Borowitz, Brent L Wood, I-Ming Chen, Richard C Harvey, Julie M Gastier-Foster, Cheryl L Willman, Stephen P Hunger, Charles G Mullighan and 1 more

Abstract read
In one paragraph

Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
139citing papers in PubMed, 1 pooled it
17.9field-weighted citation impact, top 1% 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

139 citing papers in PubMed, 1 synthesis or guideline pooled it, 241 citations in OpenAlex.

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79 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 8 institutions in 1 country.

Sarah K TasianDivision of Pediatric Hematology-Oncology, Department of Pediatrics, University of California-San Francisco, CA 94143, USA.
Michelle Y Doral
Michael J Borowitz
Brent L Wood
I-Ming Chen
Richard C Harvey
Julie M Gastier-Foster
Cheryl L Willman
Stephen P Hunger
Charles G Mullighan
Mignon L Loh
University of California, San Francisco · USUniversity of New Mexico · USJohns Hopkins University · USNationwide Children's Hospital · USNew Mexico Cancer Center · USSt. Jude Children's Research Hospital · USUniversity of Colorado Denver · USUniversity of Washington · US

Funding

COG FOREIGN ACCRUALU10CA098543 · NCI · NATIONAL CHILDHOOD CANCER FOUNDATION · PI ADAMSON, PETER C. · 2003 to 2013
$335.5M
Children's Oncology Group Statistics &Data Center GrantU10CA098413 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI ANDERSON, JAMES R · 2003 to 2013
$67.5M
Physician Scientist Training in Clinical OncologyK12CA076931 · NCI · UNIVERSITY OF PENNSYLVANIA · PI STEPHEN Patrick HUNGER, LYNN M. SCHUCHTER · 1997 to 2026
$16.5M
Support for Human Specimen Banking in NCI-Supported Cancer Clinical TrialsU24CA114766 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI RAMIREZ MILAN, NILSA DEL CARMEN · 2005 to 2014
$14.5M
Research Training in Childhood CancerT32CA128583 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Eric Alejandro Sweet-Cordero · 2007 to 2026
$6.0M
MOLECULAR SIGNATURES FOR OUTCOME PREDICTION AND THERAPEUTIC TARGETING IN ALLU01CA157937 · NCI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI HUNGER, STEPHEN PATRICK, WILLMAN, CHERYL LYNN · 2011 to 2015
$2.9M
NICHD Institutional Training for PediatriciansT32HD044331 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIERO, DONNA M. · 2003 to 2012
$2.5M
NCI NIH HHS 1T32CA128583,NCI NIH HHS 5RC2 CA14852902NCI NIH HHS K12 CA076931NCI NIH HHS K12CA076931NCI NIH HHS L40 CA142226NCI NIH HHS T32 CA128583NCI NIH HHS U01 CA157937NCI NIH HHS U10 CA098413NCI NIH HHS U10 CA098543NCI NIH HHS U10 CA98413NCI NIH HHS U24 CA114766NICHD NIH HHS 5T32HD044331NICHD NIH HHS T32 HD044331
6 · The paper itself

Abstract

Adults and children with high-risk CRLF2-rearranged acute lymphoblastic leukemia (ALL) respond poorly to current cytotoxic chemotherapy and suffer unacceptably high rates of relapse, supporting the need to use alternative therapies. CRLF2 encodes the thymic stromal lymphopoietin (TSLP) receptor, which activates cell signaling in normal lymphocytes on binding its ligand, TSLP. We hypothesized that aberrant cell signaling occurs in CRLF2-rearranged ALL and can be targeted by signal transduction inhibitors of this pathway. In a large number of primary CRLF2-rearranged ALL samples, we observed increased basal levels of pJAK2, pSTAT5, and pS6. We thus characterized the biochemical sequelae of CRLF2 and JAK alterations in CRLF2-rearranged ALL primary patient samples via analysis of TSLP-mediated signal transduction. TSLP stimulation of these leukemias further induced robust JAK/STAT and PI3K/mTOR pathway signaling. JAK inhibition abrogated phosphorylation of JAK/STAT and, surprisingly, of PI3K/mTOR pathway members, suggesting an interconnection between these signaling networks and providing a rationale for testing JAK inhibitors in clinical trials. The PI3K/mTOR pathway inhibitors rapamycin, PI103, and PP242 also inhibited activated signal transduction and translational machinery proteins of the PI3K/mTOR pathway, suggesting that signal transduction inhibitors targeting this pathway also may have therapeutic relevance for patients with CRLF2-rearranged ALL and merit further preclinical testing.

Indexed as

Gene RearrangementAdultBlotting, WesternCell ProliferationChildFlow CytometryHumansIn Situ Hybridization, FluorescencePhosphatidylinositol 3-KinasesPoint MutationPrecursor B-Cell Lymphoblastic Leukemia-LymphomaReal-Time Polymerase Chain ReactionReceptors, CytokineRNA, MessengerSignal TransductionSTAT5 Transcription FactorCRLF2 protein, humanMTOR protein, humanPhosphatidylinositol 3-KinasesReceptors, CytokineRNA, MessengerSTAT5 Transcription FactorTOR Serine-Threonine Kinases

Identifiers

PMID22685175
PMCPMC3412346
OpenAlexW2021782220

What OpenQuestion 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 OpenQuestion graph.