Evidence map›Paper›PMID 41615994›Full record

ArticlePloS one2026

Antiapoptotic BCL2 family proteins BCL-XL and MCL1 as factors predicting resistance against venetoclax plus azacitidine for patients with newly diagnosed acute myelogenous leukemia.

Yusuke Kamihara, Shohei Kikuchi, Nanako Ishikawa, Nozomi Shinomiya, Kohei Kunimoto, Ryusuke Horaguchi, Takuma Fujihira, Yoshimi Nabe, Tomoki Minemura, Kento Ono and 3 more

Abstract read
In one paragraph

Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Review
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.

Yusuke KamiharaDepartment of Hematology, Toyama University School of Medicine, Toyama, Toyama, Japan.ORCID https://orcid.org/0009-0006-5367-406X
Shohei KikuchiDepartment of Hematology, Toyama University School of Medicine, Toyama, Toyama, Japan.
Nanako IshikawaDepartment of Hematology, Toyama University School of Medicine, Toyama, Toyama, Japan.
Nozomi ShinomiyaDepartment of Hematology, Toyama University School of Medicine, Toyama, Toyama, Japan.
Kohei KunimotoDepartment of Hematology, Toyama University School of Medicine, Toyama, Toyama, Japan.
Ryusuke HoraguchiDepartment of Hematology, Toyama University School of Medicine, Toyama, Toyama, Japan.
Takuma FujihiraDepartment of Hematology, Toyama University School of Medicine, Toyama, Toyama, Japan.
Yoshimi NabeDepartment of Hematology, Toyama University School of Medicine, Toyama, Toyama, Japan.
Tomoki MinemuraDepartment of Hematology, Toyama University School of Medicine, Toyama, Toyama, Japan.
Kento OnoDepartment of Hematology, Toyama University School of Medicine, Toyama, Toyama, Japan.
Akinori WadaDepartment of Hematology, Toyama University School of Medicine, Toyama, Toyama, Japan.ORCID https://orcid.org/0000-0002-6218-519X
Nam H DangDivision of Hematology/Oncology, University of Florida, Gainesville, Florida, United States of America.
Tsutomu SatoDepartment of Hematology, Toyama University School of Medicine, Toyama, Toyama, Japan.ORCID https://orcid.org/0000-0003-2712-2713

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The combination of Venetoclax (VEN), a BCL2 inhibitor, and Azacitidine (AZA), a hypomethylating agent, is the standard treatment for acute myelogenous leukemia (AML) in patients older than 65 years who are not eligible for intensive chemotherapy. While high response rates for this treatment have been noted, it has been also reported that the anti-apoptotic BCL2 family proteins BCL-XL and MCL1 may be involved in VEN resistance. However, no study has heretofore been conducted to investigate the effectiveness of treatment and the expression of BCL-XL or MCL1 in patients treated with VEN + AZA therapy. In this study, we analyzed blasts from patients with newly diagnosed AML treated with VEN + AZA therapy by qPCR, confirmed by siRNA in cultured cell lines, and evaluated the validity of the immunostaining method. We demonstrated that BCL-XL or MCL1 was highly expressed in leukemia cells of patients who did not respond to this treatment. In addition, leukemia cells from patients who had responded to VEN + AZA but relapsed during the course of treatment showed increased expression of BCL-XL or MCL1 compared to pre-treatment levels. Furthermore, downregulation of BCL-XL expression in a VEN-resistant AML cell line with siRNA increased sensitivity to VEN. On the other hand, the expression of BCL-XL and MCL1 in leukemia cells could be easily semi-quantified by immunostaining, with these results correlating with those obtained by qPCR. These results indicate that immunostaining for BCL-XL and MCL1 upon bone marrow examination at diagnosis not only can predict susceptibility to VEN + AZA therapy, but may also be useful for patient stratification for VEN + AZA treatment in the future.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsAzacitidinebcl-X ProteinBridged Bicyclo Compounds, HeterocyclicDrug Resistance, NeoplasmLeukemia, Myeloid, AcuteMyeloid Cell Leukemia Sequence 1 ProteinSulfonamidesAgedAged, 80 and overApoptosisCell Line, TumorFemaleHumansMaleMiddle AgedAzacitidineBCL2L1 protein, humanbcl-X ProteinBridged Bicyclo Compounds, HeterocyclicMCL1 protein, humanMyeloid Cell Leukemia Sequence 1 ProteinSulfonamidesvenetoclax

Identifiers

PMID41615994
PMCPMC12857986

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.