Evidence map›Paper›PMID 35476984›Full record

ArticleCell reports2022

Hypoxic, glycolytic metabolism is a vulnerability of B-acute lymphoblastic leukemia-initiating cells.

Vivian Morris, Dahai Wang, Zhiheng Li, William Marion, Travis Hughes, Patricia Sousa, Taku Harada, Shannan Ho Sui, Sergey Naumenko, Jérémie Kalfon and 18 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

9 citing papers in PubMed, 15 citations in OpenAlex.

  1. A guide to B cell metabolism.Nature reviews. Immunology · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Metabolic dependencies of acute myeloid leukemia stem cells.International journal of hematology · 2024
    Review
  6. Article
  7. Review
  8. Review
  9. 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

28 authors at 5 institutions in 3 countries.

Vivian MorrisStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA.
Dahai WangStem Cell Transplantation Program, Department of Hematology, Boston Children's Hospital, Boston, MA 02115, USA.
Zhiheng LiStem Cell Transplantation Program, Department of Hematology, Boston Children's Hospital, Boston, MA 02115, USA.
William MarionStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA.
Travis HughesKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA.
Patricia SousaStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA.
Taku HaradaCancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02115, USA.
Shannan Ho SuiHarvard Chan Bioinformatics Core, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Sergey NaumenkoHarvard Chan Bioinformatics Core, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Jérémie KalfonBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Prerana SensharmaStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Stem Cell Transplantation Program, Department of Hematology, Boston Children's Hospital, Boston, MA 02115, USA.
Marcelo FalchettiGraduate Program of Pharmacology, Center for Biological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina 88040-900, Brazil.
Renan Vinicius da SilvaGraduate Program of Pharmacology, Center for Biological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina 88040-900, Brazil.
Tito CandelliPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Pauline SchneiderPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Thanasis MargaritisPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Frank C P HolstegePrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Yana PikmanHarvard Medical School, Boston, MA 02115, USA; Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02115, USA.
Marian HarrisHarvard Medical School, Boston, MA 02115, USA; Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA.
Ronald W StamPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Stuart H OrkinHarvard Medical School, Boston, MA 02115, USA; Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA.
Angela N KoehlerKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Alex K ShalekKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Trista E NorthStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
Maxim PimkinBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02115, USA.
George Q DaleyStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
Edroaldo Lummertz da RochaDepartment of Microbiology, Immunology and Parasitology, Federal University of Santa Catarina, Florianópolis Santa Catarina 88040-900, Brazil.
R Grant RoweStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Stem Cell Transplantation Program, Department of Hematology, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02115, USA. Electronic address: grant_rowe@dfci.harvard.edu.
Boston Children's Hospital · USBroad Institute · USPrincess Máxima Center · NLUniversidade Federal de Santa Catarina · BRHarvard University · US

Funding

The Harvard Clinical and Translational Science CenterUL1TR002541 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2018 to 2022
$93.0M
Stem cells for therapeutics discovery in genetic blood disordersU01HL134812 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI DALEY, GEORGE Q, LIPTON, JEFFREY M · 2016 to 2022
$8.3M
Targeting mitochondrial one carbon folate metabolism for novel T-cell acute lymphoblastic leukemia therapyK08CA222684 · NCI · DANA-FARBER CANCER INST · PI PIKMAN, YANA · 2018 to 2022
$886k
Role of the Lin28b/let-7 axis in the maturation of hematopoietic progenitor cellsK08DK114527 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI ROWE, ROBERT GRANT · 2017 to 2021
$704k
NCATS NIH HHS UL1 TR002541NCI NIH HHS K08 CA222684NHLBI NIH HHS U01 HL134812NIDDK NIH HHS K08 DK114527
6 · The paper itself

Abstract

High-risk forms of B-acute lymphoblastic leukemia (B-ALL) remain a therapeutic challenge. Leukemia-initiating cells (LICs) self-renew and spark relapse and therefore have been the subject of intensive investigation; however, the properties of LICs in high-risk B-ALL are not well understood. Here, we use single-cell transcriptomics and quantitative xenotransplantation to understand LICs in MLL-rearranged (MLL-r) B-ALL. Compared with reported LIC frequencies in acute myeloid leukemia (AML), engraftable LICs in MLL-r B-ALL are abundant. Although we find that multipotent, self-renewing LICs are enriched among phenotypically undifferentiated B-ALL cells, LICs with the capacity to replenish the leukemic cellular diversity can emerge from more mature fractions. While inhibiting oxidative phosphorylation blunts blast proliferation, this intervention promotes LIC emergence. Conversely, inhibiting hypoxia and glycolysis impairs MLL-r B-ALL LICs, providing a therapeutic benefit in xenotransplantation systems. These findings provide insight into the aggressive nature of MLL-r B-ALL and provide a rationale for therapeutic targeting of hypoxia and glycolysis.

Indexed as

Leukemia, Myeloid, AcutePrecursor Cell Lymphoblastic Leukemia-LymphomaGlycolysisHumansHypoxiaCP: CancerCP: Metabolismleukemiametabolismstem cell

Identifiers

PMID35476984
PMCPMC9099058
OpenAlexW4224434557

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.