Evidence map›Paper›PMID 27063598›Full record

ArticleLeukemia2016

Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia.

V Madan, P Shyamsunder, L Han, A Mayakonda, Y Nagata, J Sundaresan, D Kanojia, K Yoshida, S Ganesan, N Hattori and 42 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 64 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 1 pooled it
8.5field-weighted citation impact, top 2% 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

64 citing papers in PubMed, 1 synthesis or guideline pooled it, 136 citations in OpenAlex.

  1. Pooled it
  2. The comprehensive landscape ofHaematologica · 2026
    Article
  3. Review
  4. Predictors of Early Death in Acute Promyelocytic Leukemia.Medical sciences (Basel, Switzerland) · 2025
    Review
  5. Article
  6. Article
  7. Recent progress in AML with recurrent genetic abnormalities.International journal of hematology · 2024
    Review
  8. Review
  9. Review
  10. Review
  11. Identification of a NovelTurkish journal of haematology : official journal of Turkish Society of Haematology · 2024
    Article
  12. Review
  13. Article
  14. Article
  15. Function of PML-RARA in Acute Promyelocytic Leukemia.Advances in experimental medicine and biology · 2024
    Review
  16. Article
  17. The PML hub: An emerging actor of leukemia therapies.The Journal of experimental medicine · 2023
    Article
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

52 authors at 20 institutions in 9 countries.

V MadanCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
P ShyamsunderCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
L HanCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
A MayakondaCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
Y NagataDepartment of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
J SundaresanCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
D KanojiaCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
K YoshidaDepartment of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
S GanesanDepartment of Haematology, Christian Medical College, Vellore, India.
N HattoriCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
N FultonSection of Hematology/Oncology, University of Chicago, Chicago, IL, USA.
K-T TanCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
T AlpermannMunich Leukemia Laboratory (MLL), Munich, Germany.
M-C KuoDivision of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.
S RostamiHematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
J MatthewsSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
M SanadaDepartment of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
L-Z LiuCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
Y ShiraishiLaboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
S MiyanoLaboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
E ChendamaraiDepartment of Haematology, Christian Medical College, Vellore, India.
H-A HouDepartment of Internal Medicine, National Taiwan University, Medical College and Hospital, Taipei, Taiwan.
G MalnassySection of Hematology/Oncology, University of Chicago, Chicago, IL, USA.
T MaDivision of Hematology, Oncology and Stem Cell Transplantation, Department of Internal Medicine, University of Freiburg Medical Center, Freiburg, Germany.
M GargCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
L-W DingCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
Q-Y SunCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
W ChienCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
T IkezoeDepartment of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
M LillCedars-Sinai Medical Center, Division of Hematology/Oncology, UCLA School of Medicine, Los Angeles, CA, USA.
A BiondiPaediatric Haematology-Oncology Department and 'Tettamanti' Research Centre, Milano-Bicocca University, 'Fondazione MBBM', San Gerardo Hospital, Monza, Italy.
R A LarsonDepartment of Medicine, University of Chicago Comprehensive Cancer Center, Chicago, IL, USA.
B L PowellDepartment of Internal Medicine, Section on Hematology and Oncology, Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC, USA.
M LübbertDivision of Hematology, Oncology and Stem Cell Transplantation, Department of Internal Medicine, University of Freiburg Medical Center, Freiburg, Germany.
W J ChngCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
H-F TienDepartment of Internal Medicine, National Taiwan University, Medical College and Hospital, Taipei, Taiwan.
M HeuserDepartment of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
A GanserDepartment of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
M Koren-MichowitzSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
S M KornblauSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
H M KantarjianSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
D NowakDepartment of Hematology and Oncology, University Hospital Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
W-K HofmannDepartment of Hematology and Oncology, University Hospital Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
H YangCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
W StockSection of Hematology/Oncology, University of Chicago, Chicago, IL, USA.
A GhavamzadehHematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
K AlimoghaddamHematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
T HaferlachMunich Leukemia Laboratory (MLL), Munich, Germany.
S OgawaDepartment of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
L-Y ShihDivision of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.
V MathewsDepartment of Haematology, Christian Medical College, Vellore, India.
H P KoefflerCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
National University Cancer Institute, Singapore · SGNational University of Singapore · SGKyoto University · JPUniversity of Chicago · USChristian Medical College & Hospital · INTehran University of Medical Sciences · IRThe University of Texas MD Anderson Cancer Center · USChang Gung Memorial Hospital · TWMedizinische Hochschule Hannover · DEMunich Leukemia Laboratory (Germany) · DENational Taiwan University Hospital · TWThe University of Tokyo · JPCedars-Sinai Medical Center · USHeidelberg University · DEKōchi University · JPTel Aviv University · ILUniversity Hospital Heidelberg · DEUniversity Medical Center Freiburg · DEUniversity of Freiburg · DEUniversity of Milano-Bicocca · IT

Funding

CANCER AND LEUKEMIA GROUP B MINORITY SATELLITE SUPPLEMENU10CA031946 · NCI · UNIVERSITY OF CHICAGO · PI BERTAGNOLLI, MONICA M · 1985 to 2013
$158.4M
REGULATION OF HEMATOPOIETIC CYTOKINESR01CA026038 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KOEFFLER, HAROLD PHILLIP · 1985 to 2013
$4.7M
DBT-Wellcome Trust India Alliance IA/S/11/2500267NCI NIH HHS R01 CA026038NCI NIH HHS U10 CA031946Wellcome Trust
6 · The paper itself

Abstract

Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by differentiation block at the promyelocyte stage. Besides the presence of chromosomal rearrangement t(15;17), leading to the formation of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis of primary and relapse APL to identify somatic alterations, which cooperate with PML-RARA in the pathogenesis of APL. We explored the mutational landscape using whole-exome (n=12) and subsequent targeted sequencing of 398 genes in 153 primary and 69 relapse APL. Both primary and relapse APL harbored an average of eight non-silent somatic mutations per exome. We observed recurrent alterations of FLT3, WT1, NRAS and KRAS in the newly diagnosed APL, whereas mutations in other genes commonly mutated in myeloid leukemia were rarely detected. The molecular signature of APL relapse was characterized by emergence of frequent mutations in PML and RARA genes. Our sequencing data also demonstrates incidence of loss-of-function mutations in previously unidentified genes, ARID1B and ARID1A, both of which encode for key components of the SWI/SNF complex. We show that knockdown of ARID1B in APL cell line, NB4, results in large-scale activation of gene expression and reduced in vitro differentiation potential.

Indexed as

Cell DifferentiationDNA-Binding ProteinsDNA Mutational AnalysisExomeGene Expression ProfilingHumansLeukemia, Promyelocytic, AcuteNuclear ProteinsRecurrenceTranscription FactorsARID1A protein, humanARID1B protein, humanDNA-Binding ProteinsNuclear ProteinsTranscription Factors

Identifiers

PMID27063598
PMCPMC4972641
OpenAlexW2329310651

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.