Evidence map›Paper›PMID 21993666›Full record

ArticleHaematologica2012

CD34(+)/CD38(-) stem cells in chronic myeloid leukemia express Siglec-3 (CD33) and are responsive to the CD33-targeting drug gemtuzumab/ozogamicin.

Harald Herrmann, Sabine Cerny-Reiterer, Karoline V Gleixner, Katharina Blatt, Susanne Herndlhofer, Werner Rabitsch, Eva Jäger, Gerlinde Mitterbauer-Hohendanner, Berthold Streubel, Edgar Selzer and 3 more

Open access · goldAbstract read
In one paragraph

Article in Haematologica, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

39 citing papers in PubMed, 66 citations in OpenAlex.

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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

13 authors at 2 institutions in 1 country.

Harald HerrmannLudwig Boltzmann Cluster Oncology, Vienna, Austria.
Sabine Cerny-Reiterer
Karoline V Gleixner
Katharina Blatt
Susanne Herndlhofer
Werner Rabitsch
Eva Jäger
Gerlinde Mitterbauer-Hohendanner
Berthold Streubel
Edgar Selzer
Ilse Schwarzinger
Wolfgang R Sperr
Peter Valent
Medical University of Vienna · ATLudwig Boltzmann Cluster for Cardiovascular Research · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCD33 is a well-known stem cell target in acute myeloid leukemia. So far, however, little is known about expression of CD33 on leukemic stem cells in chronic leukemias. DESIGN AND

methodsWe analyzed expression of CD33 in leukemic progenitors in chronic myeloid leukemia by multi-color flow cytometry and quantitative polymerase chain reaction. In addition, the effects of a CD33-targeting drug, gemtuzumab/ozogamicin, were examined.

resultsAs assessed by flow cytometry, stem cell-enriched CD34(+)/CD38(-)/CD123(+) leukemic cells expressed significantly higher levels of CD33 compared to normal CD34(+)/CD38(-) stem cells. Moreover, highly enriched leukemic CD34(+)/CD38(-) cells (>98% purity) displayed higher levels of CD33 mRNA. In chronic phase patients, CD33 was found to be expressed invariably on most or all stem cells, whereas in accelerated or blast phase of the disease, the levels of CD33 on stem cells varied from donor to donor. The MDR1 antigen, supposedly involved in resistance against ozogamicin, was not detectable on leukemic CD34(+)/CD38(-) cells. Correspondingly, gemtuzumab/ozogamicin produced growth inhibition in leukemic progenitor cells in all patients tested. The effects of gemtuzumab/ozogamicin were dose-dependent, occurred at low concentrations, and were accompanied by apoptosis in suspension culture. Moreover, the drug was found to inhibit growth of leukemic cells in a colony assay and long-term culture-initiating cell assay. Finally, gemtuzumab/ozogamicin was found to synergize with nilotinib and bosutinib in inducing growth inhibition in leukemic cells.

conclusionsCD33 is expressed abundantly on immature CD34(+)/CD38(-) stem cells and may serve as a stem cell target in chronic myeloid leukemia.

Indexed as

ADP-ribosyl Cyclase 1AdultAgedAged, 80 and overAminoglycosidesAntibodies, Monoclonal, HumanizedAntigens, CDAntigens, CD34Antigens, Differentiation, MyelomonocyticCell ProliferationFemaleGemtuzumabGene Expression Regulation, NeoplasticHumansLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMaleADP-ribosyl Cyclase 1AminoglycosidesAntibodies, Monoclonal, HumanizedAntigens, CDAntigens, CD34Antigens, Differentiation, MyelomonocyticCD33 protein, humanGemtuzumabSialic Acid Binding Ig-like Lectin 3

Identifiers

PMID21993666
PMCPMC3269481
OpenAlexW2131999851

What OpenQuestion holds

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Registered trials

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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.