Evidence map›Paper›PMID 32005797›Full record

ArticleBlood cancer journal2020

SYK is activated by mutated MYD88 and drives pro-survival signaling in MYD88 driven B-cell lymphomas.

Manit Munshi, Xia Liu, Jiaji G Chen, Lian Xu, Nickolas Tsakmaklis, Maria G Demos, Amanda Kofides, Maria Luisa Guerrera, Cristina Jimenez, Gloria G Chan and 14 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Blood cancer journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

28 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. The Direction of Modern Therapies in Waldenström Macroglobulinaemia.Journal of cellular and molecular medicine · 2025
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. International journal of molecular sciences · 2022
    Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. 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

24 authors at 3 institutions in 1 country.

Manit MunshiBing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Xia LiuBing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Jiaji G ChenBing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Lian XuBing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Nickolas TsakmaklisBing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Maria G DemosBing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Amanda KofidesBing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Maria Luisa GuerreraBing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Cristina JimenezBing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Gloria G ChanBing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Zachary R HunterBing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1689-1691
M Lia PalombaLymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Kimon V ArgyropoulosLymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Kirsten MeidBing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Andrew KeezerBing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Joshua GustineBing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Toni DubeauBing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Jorge J CastilloBing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9490-7532
Christopher J PattersonBing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Jinhua WangDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Sara J BuhrlageDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Nathanael S GrayDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Steven P TreonBing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. steven_treon@dfci.harvard.edu.
Guang YangBing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Dana-Farber Cancer Institute · USHarvard University · USMemorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Trageting the Multiple Myeloma EpigenomeP50CA100707 · NCI · DANA-FARBER CANCER INSTITUTE · PI ANDERSON, KENNETH C., MUNSHI, NIKHIL C. · 2003 to 2023
$45.0M
NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA100707
6 · The paper itself

Abstract

Activating MYD88 mutations promote pro-survival signaling through BTK and HCK, both targets of ibrutinib. Despite high response rates, complete responses to ibrutinib are lacking, and other MYD88 triggered pro-survival pathways may contribute to primary drug resistance. B-cell receptor (BCR) signaling has been observed in lymphomas driven by mutated MYD88, even without activating the BCR pathway mutations. We identified activated SYK (p-SYK), a component of BCR in complex with MYD88 in MYD88-mutated WM and ABC DLBCL lymphoma cells. Confocal microscopy confirmed co-localization of MYD88 with SYK in MYD88-mutated cells. Knockdown of MYD88 or use of a MYD88 signaling inhibitor abrogated SYK activation, while expression of mutated but not wild-type MYD88 amplified p-SYK in MYD88-mutated and wild-type lymphoma cells. Knockdown of SYK or use of inhibitors targeting SYK blocked p-STAT3 and p-AKT signaling in MYD88-mutated cells. Cell viability analysis showed that combining ibrutinib and SYK inhibitors triggered synthetic killing of MYD88-mutated lymphoma cells. Our findings extend the spectrum of mutated MYD88 pro-survival signaling to include SYK directed BCR cross talk in MYD88-mutated lymphomas. Targeting SYK in combination with ibrutinib produces synthetic lethality, providing a framework for the clinical investigation of ibrutinib with SYK inhibitors in MYD88-mutated lymphomas.

Indexed as

Cell Line, TumorHumansLymphoma, Large B-Cell, DiffuseMutationMyeloid Differentiation Factor 88Signal TransductionSyk KinaseMYD88 protein, humanMyeloid Differentiation Factor 88Syk KinaseSYK protein, human

Identifiers

PMID32005797
PMCPMC6994488
OpenAlexW3003862081

What Socratic 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 Socratic graph.