Identification of an alternative CD20 transcript variant in B-cell malignancies coding for a novel protein associated to rituximab resistance.

Carole Henry; Marina Deschamps; Pierre-Simon Rohrlich; Jean-René Pallandre; Jean-Paul Rémy-Martin; Mary Callanan; Alexandra Traverse-Glehen; Camille Grandclément; Francine Garnache-Ottou; Remy Gressin; Eric Deconinck; Gilles Salles; Eric Robinet; Pierre Tiberghien; Christophe Borg; Christophe Ferrand

doi:10.1182/blood-2009-06-229112

Identification of an alternative CD20 transcript variant in B-cell malignancies coding for a novel protein associated to rituximab resistance.

Carole Henry ¹ Marina Deschamps ¹ Pierre-Simon Rohrlich ¹ Jean-René Pallandre ¹ Jean-Paul Rémy-Martin ¹ Mary Callanan ² Alexandra Traverse-Glehen ³ Camille Grandclément ¹ Francine Garnache-Ottou ^{1, 3} Remy Gressin ⁴ Eric Deconinck ^{1, 5} Gilles Salles ³ Eric Robinet ⁶ Pierre Tiberghien ^{1, 7} Christophe Borg ^{1, 7} Christophe Ferrand ^{1, 8}

1 HOTE GREFFON - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)

2 INSERM U823, équipe 7 (Voies Oncogéniques Des Hémopathies Malignes)

INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble

3 LBMC - Laboratoire de Biologie Moléculaire de la Cellule

4 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble

5 Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang

6 Interaction virus-hôte et maladies du foie

7 Service d'oncologie Médicale

8 Laboratoire de biologie moléculaire

Abstract : Human CD20 is a B-cell lineage-specific marker expressed by normal and leukemic B cells from the pre-B to the plasma-cell stages and is a target for rituximab (RTX) immunotherapy. A CD20 reverse transcriptase-polymerase chain reaction (PCR) on B-cell lines cDNA yielded a short PCR product (DeltaCD20) corresponding to a spliced mRNA transcript linking the exon 3 and exon 7 ends. We established here that this novel, alternatively spliced CD20 transcript is expressed and detectable at various levels in leukemic B cells, lymphoma B cells, in vivo tonsil- or in vitro CD40L-activated B cells, and Epstein-Barr virus (EBV)-transformed B cells, but not in resting CD19(+)- or CD20(+)-sorted B cells from peripheral blood or bone marrow of healthy donors. The truncated CD20 sequence is within the reading frame, codes a protein of 130 amino acids ( approximately 15-17 kDa) lacking large parts of the 4 transmembrane segments, suggesting that DeltaCD20 is a nonanchored membrane protein. We demonstrated the translation into a DeltaCD20 protein which is associated with the membrane CD20 protein and showed its involvement in RTX resistance. Study of patient samples before and after RTX resistance or escape confirms our in vitro findings.

Type de document :

Article dans une revue

Blood, American Society of Hematology, 2010, 115 (12), pp.2420-9. 〈10.1182/blood-2009-06-229112〉

Domaine :

Sciences du Vivant [q-bio] / Immunologie

Liste complète des métadonnées

http://www.hal.inserm.fr/inserm-00484312
Contributeur : Philippe Saas <>
Soumis le : mardi 18 mai 2010 - 11:59:41
Dernière modification le : lundi 9 juillet 2018 - 13:12:02

Identification of an alternative CD20 transcript variant in B-cell malignancies coding for a novel protein associated to rituximab resistance.

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Identification of an alternative CD20 transcript variant in B-cell malignancies coding for a novel protein associated to rituximab resistance.

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