Evidence map›Paper›PMID 12200686›Full record

ArticleLeukemia2002

Stromal cells prevent apoptosis of AML cells by up-regulation of anti-apoptotic proteins.

M Konopleva, S Konoplev, W Hu, A Y Zaritskey, B V Afanasiev, M Andreeff

Abstract read
PubMed Publisher
In one paragraph

Article in Leukemia, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 207 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
207citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 9% 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

207 citing papers in PubMed, 1 synthesis or guideline pooled it, 386 citations in OpenAlex.

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147 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

6 authors at 2 institutions in 2 countries.

M KonoplevaSection of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
S Konoplev
W Hu
A Y Zaritskey
B V Afanasiev
M Andreeff
The University of Texas MD Anderson Cancer Center · USFirst Pavlov State Medical University of St. Petersburg · RU

Funding

THE THERAPY OF AMLP01CA055164 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI THOMAS, MATTIE J · 1992 to 2011
$25.3M
NCI NIH HHS P01 CA16672NCI NIH HHS P01 CA55164
6 · The paper itself

Abstract

The aim of this study was to study interactions between stromal bone marrow microenvironment and leukemic cells. We tested the hypothesis that stromal cells prevent apoptosis of AML cells by up-regulating anti-apoptotic proteins in leukemic blasts. In HL-60 and NB-4 cells, serum deprivation- and ara-C-induced apoptosis was diminished when cells were cocultured with murine MS-5 stromal cells (P < 0.02). This effect was reproduced with conditioned medium from MS-5 cells. Cocultivation with stromal cells induced Bcl-2 expression levels, both by PCR analysis and flow cytometry. In primary AML (n = 14), ara-C-induced apoptosis was significantly lower in cells cocultured with MS-5 cells than in controls (P < 0.001). This effect was partially preserved when leukemic cells were separated from stromal cells by a microporous insert (in 5/9 samples, P = 0.04). In addition, Bcl-2 levels were significantly higher in stroma-supported than in control CD34(+) AML cells (P < 0.01). Bcl-X(L) levels were higher in 5/7 samples grown on stromal layers. Of note, in AML patients resistant to induction chemotherapy (n = 6), Bcl-2 increased significantly after cultivation with stromal cells, but no such increase was noted in cells from chemotherapy-sensitive patients. In conclusion, MS-5 stromal cells prevented apoptosis in HL-60 cells and in primary AML blasts via modulation of Bcl-2 family proteins. The observed association of high Bcl-2 expression in stroma-supported AML blasts in vitro with resistance to chemotherapy in vivo suggests that the same mechanisms may be operational in vivo.

Indexed as

Organic ChemicalsAcute DiseaseAdultAgedAged, 80 and overAnimalsAntimetabolites, AntineoplasticApoptosisBone Marrow CellsCell AdhesionCell DivisionCulture Media, Serum-FreeCytarabineDNA PrimersFemaleFluorescent DyesAntimetabolites, AntineoplasticCulture Media, Serum-FreeCytarabineDNA PrimersFluorescent DyesOrganic ChemicalsPKH 26Proto-Oncogene Proteins c-bcl-2RNA, Neoplasm

Identifiers

PMID12200686
OpenAlexW2321953223

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.