MMS22L is a novel key actor of normal and pathological erythropoiesis

Elia Colin; Ivan Ferrer-vicens; Dror Brook; Mohammad Salma; Charlotte Andrieu-soler; Elisa Bayard; Alicia Fernandes; Chantal Brouzes; Carine Lefevre; Romain Duval; Michael Dussiot; Thiago Trovati; Genevieve Courtois; Slim Azouzi; Mohammed Zarhrate; Anne Lambilliotte; Sophie Park; Benjamin Carpentier; Martin Colard; Sandra Manceau; Despina Moshous; Patrick Mayeux; Emilie-fleur Gautier; Annarita Miccio; Jean Soulier; William Vainchenker; Liran Shlush; Lydie Da Costa; Jan Frayne; Eric Soler; Olivier Hermine; Lucile Couronne

doi:10.1002/hem3.70264

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MMS22L is a novel key actor of normal and pathological erythropoiesis

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MMS22L is a novel key actor of normal and pathological erythropoiesis

Elia Colin, Ivan Ferrer-vicens, Dror Brook, Mohammad Salma, Charlotte Andrieu-soler, Elisa Bayard, Alicia Fernandes, Chantal Brouzes, Carine Lefevre, Romain Duval, …

HemaSphere, Vol.9(12), pp.e70264-n/a

12/2025

DOI: https://doi.org/10.1002/hem3.70264

PMID: 41446536

Résumé

Hematology

Life Sciences & Biomedicine

Science & Technology

The emergence of next-generation sequencing techniques has led to the genetic characterization of numerous congenital erythroid disorders, emphasizing crucial pathways in both normal and pathological erythropoiesis. In this study, whole exome sequencing of a single patient with atypical congenital pure red cell aplasia revealed a mutation in the CDAN1 gene, typically associated with congenital dyserythropoietic anemia type 1 (CDAI), together with a previously unreported mutation in the MMS22L gene. Combined mms22l and cdan1 haploinsufficiency results in severe anemia in a zebrafish model. In human erythroid progenitors, loss of MMS22L leads to proliferation and differentiation arrest associated with activation of the p53 pathway and global epigenetic alterations, showing that MMS22L plays an indispensable role in erythropoiesis. Furthermore, MMS22L and CDAN1 are involved in the same protein complex whose nuclear import is mediated by the importin 4 (IPO4) protein, and MMS22L nuclear import is impaired in CDAI patients due to a defective interaction between CDAN1 and IPO4. Overall, through the genetic description of a single case characterized by digenic inheritance, we identified MMS22L as a novel key factor in erythropoiesis and brought new insights into normal erythropoiesis regulation and CDAI pathophysiology.

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Titre: MMS22L is a novel key actor of normal and pathological erythropoiesis
Créateurs - sans rôle: Elia Colin - Univ Paris Cite, Imagine Inst, Lab cellular & Mol Mech hematol disorders & therap, INSERM,UMR S 1163, Paris, France
Ivan Ferrer-vicens
Dror Brook - Weizmann Inst Sci, Dept Appl Math & Comp Sci, Rehovot, Israel
Mohammad Salma - Univ Paris Cite, Initiat IdEx Globule Rouge Excellence InIdex GR Ex, Paris, France
Charlotte Andrieu-soler
Elisa Bayard - Univ Paris Cite, Imagine Inst, Lab cellular & Mol Mech hematol disorders & therap, INSERM,UMR S 1163, Paris, France
Alicia Fernandes - SFR Necker, VVTG Platform, Paris, France
Chantal Brouzes - Necker Childrens Hosp, Assistance Publ Hop Paris, Lab Oncohematol, Paris, France
Carine Lefevre - Univ Paris Cite, Initiat IdEx Globule Rouge Excellence InIdex GR Ex, Paris, France
Romain Duval - Univ Paris Cite, Paris, France
Michael Dussiot - Univ Paris Cite, Imagine Inst, Lab cellular & Mol Mech hematol disorders & therap, INSERM,UMR S 1163, Paris, France
Thiago Trovati - Univ Paris Cite, Imagine Inst, Lab cellular & Mol Mech hematol disorders & therap, INSERM,UMR S 1163, Paris, France
Genevieve Courtois - Univ Paris Cite, Imagine Inst, Lab cellular & Mol Mech hematol disorders & therap, INSERM,UMR S 1163, Paris, France
Slim Azouzi - Univ Paris Cite, Initiat IdEx Globule Rouge Excellence InIdex GR Ex, Paris, France
Mohammed Zarhrate - Paris Descartes Sorbonne Univ Paris Cite, Inst Imagine Struct Federat Rech Necker, Genom Core Facil, INSERM,U1163, Paris, France
Anne Lambilliotte - Lille Univ Hosp, Pediat Hematol, Lille, France
Sophie Park - Inserm
Benjamin Carpentier - Lille Catholic Univ, St Vincent Paul Hosp, Hematol Dept, Lille, France
Martin Colard - Univ Paris Cite, Imagine Inst, Lab cellular & Mol Mech hematol disorders & therap, INSERM,UMR S 1163, Paris, France
Sandra Manceau - Univ Paris Cite, Initiat IdEx Globule Rouge Excellence InIdex GR Ex, Paris, France
Despina Moshous - Univ Paris Cite, Necker Childrens Hosp,Dept Pediat Immunol Hematol, Assistance Publ Hop Paris,Inst Imagine, Lab Genome Dynam Immune Syst, Paris, France
Patrick Mayeux - Univ Paris Cite, Initiat IdEx Globule Rouge Excellence InIdex GR Ex, Paris, France
Emilie-fleur Gautier - Univ Paris Cite, Initiat IdEx Globule Rouge Excellence InIdex GR Ex, Paris, France
Annarita Miccio - Univ Paris Cite, Imagine Inst, Lab chromatin & gene regulat Dev, INSERM,U1163, Paris, France
Jean Soulier - Univ Paris Cite, St Louis Hosp, Assistance Publ Hop Paris,St Louis Res Inst, INSERM,U944,Hematol Lab, Paris, France
William Vainchenker - Univ Paris Cite, Initiat IdEx Globule Rouge Excellence InIdex GR Ex, Paris, France
Liran Shlush - Weizmann Inst Sci, Dept Mol Cell Biol, Rehovot, Israel
Lydie Da Costa - Univ Paris Cite, Initiat IdEx Globule Rouge Excellence InIdex GR Ex, Paris, France
Jan Frayne - Univ Bristol, Sch Biochem, Bristol, England
Eric Soler - Univ Paris Cite, Initiat IdEx Globule Rouge Excellence InIdex GR Ex, Paris, France
Olivier Hermine - Univ Paris Cite, Imagine Inst, Lab cellular & Mol Mech hematol disorders & therap, INSERM,UMR S 1163, Paris, France
Lucile Couronne - Univ Paris Cite, Imagine Inst, Lab cellular & Mol Mech hematol disorders & therap, INSERM,UMR S 1163, Paris, France
Détails de publication: HemaSphere, Vol.9(12), pp.e70264-n/a
Éditeur: Wiley
Nombre de pages: 13
Note de subvention: ANR-18-IDEX-0001 / Idex Universit Paris Cit, InIdex GR-Ex
Identifiants: 99153929409311
Unité académique: Institut de Génétique Moléculaire de Montpellier - IGMM
Langue: English
Type de ressource: Journal article