Evidence map›Paper›PMID 37370755›Full record

ArticleCancers2023

Role of Intracellular Drug Disposition in the Response of Acute Myeloid Leukemia to Cytarabine and Idarubicin Induction Chemotherapy.

Gabriela Rodríguez-Macías, Oscar Briz, Candela Cives-Losada, María C Chillón, Carolina Martínez-Laperche, Ibon Martínez-Arranz, Ismael Buño, Marcos González-Díaz, José L Díez-Martín, Jose J G Marin and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.7field-weighted citation impact, top 14% 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

7 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
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 5 institutions in 1 country.

Gabriela Rodríguez-MacíasExperimental Hepatology and Drug Targeting (HEVEPHARM) Group, Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain.
Oscar BrizExperimental Hepatology and Drug Targeting (HEVEPHARM) Group, Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain.ORCID 0000-0001-6891-1554
Candela Cives-LosadaExperimental Hepatology and Drug Targeting (HEVEPHARM) Group, Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain.ORCID 0000-0003-0430-838X
María C ChillónHematology, Biomedical Research Institute of Salamanca, Salamanca University Hospital, 37007 Salamanca, Spain.ORCID 0000-0003-1624-6059
Carolina Martínez-LapercheDepartment of Hematology, Gregorio Marañón General University Hospital, 28007 Madrid, Spain.
Ibon Martínez-ArranzOWL Metabolomics, Bizkaia Technology Park, 48160 Derio, Spain.
Ismael BuñoDepartment of Hematology, Gregorio Marañón General University Hospital, 28007 Madrid, Spain.ORCID 0000-0003-4931-9170
Marcos González-DíazHematology, Biomedical Research Institute of Salamanca, Salamanca University Hospital, 37007 Salamanca, Spain.
José L Díez-MartínDepartment of Hematology, Gregorio Marañón General University Hospital, 28007 Madrid, Spain.
Jose J G MarinExperimental Hepatology and Drug Targeting (HEVEPHARM) Group, Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain.ORCID 0000-0003-1186-6849
Rocio I R MaciasExperimental Hepatology and Drug Targeting (HEVEPHARM) Group, Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain.ORCID 0000-0002-4748-0326
Universidad de Salamanca · ESInstituto de Salud Carlos III · ESUniversidad Complutense de Madrid · ESEuskadiko Parke Teknologikoa · ESHospital General Universitario Gregorio Marañón · ES

Funding

Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III PI19/00819Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III PI20/00189Fundación Mutua Madrileña Call 2015Junta de Castilla y León BIO/SA52/15
6 · The paper itself

Abstract

Despite its often low efficacy and high toxicity, the standard treatment for acute myeloid leukemia (AML) is induction chemotherapy with cytarabine and idarubicin. Here, we have investigated the role of transporters and drug-metabolizing enzymes in this poor outcome. The expression levels (RT-qPCR) of potentially responsible genes in blasts collected at diagnosis were related to the subsequent response to two-cycle induction chemotherapy. The high expression of uptake carriers (ENT2), export ATP-binding cassette (ABC) pumps (MDR1), and enzymes (DCK, 5-NT, and CDA) in the blasts was associated with a lower response. Moreover, the sensitivity to cytarabine in AML cell lines was associated with ENT2 expression, whereas the expression of ABC pumps and enzymes was reduced. No ability of any AML cell line to export idarubicin through the ABC pumps, MDR1 and MRP, was found. The exposure of AML cells to cytarabine or idarubicin upregulated the detoxifying enzymes (5-NT and DCK). In AML patients, 5-NT and DCK expression was associated with the lack of response to induction chemotherapy (high sensitivity and specificity). In conclusion, in the blasts of AML patients, the reduction of the intracellular concentration of the active metabolite of cytarabine, mainly due to the increased expression of inactivating enzymes, can determine the response to induction chemotherapy.

Indexed as

AMLblood cancerchemoresistancechemotherapyprognosis

Identifiers

PMID37370755
PMCPMC10296567
OpenAlexW4380354410

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.