AUTHOR=Saettini Francesco , Coliva Tiziana Angela , Vendemini Francesca , Galbiati Marta , Bugarin Cristina , Masetti Riccardo , Moratto Daniele , Chiarini Marco , Guerra Fabiola , Iascone Maria , Badolato Raffaele , Cazzaniga Giovanni , Niemeyer Charlotte , Flotho Christian , Biondi Andrea 

TITLE=Abnormal B-Cell Maturation and Increased Transitional B Cells in CBL Syndrome

JOURNAL=Frontiers in Pediatrics

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.935951

DOI=10.3389/fped.2022.935951

ISSN=2296-2360

ABSTRACT=<p>CBL syndrome is a Noonan-like RASopathy with heterogeneous clinical phenotype and predisposition to juvenile myelomonocytic leukemia (JMML). Here we describe two patients with identical germline <italic>CBL</italic> mutation and clinical and immune-hematological overlapping features with autoimmune lymphoproliferative syndrome (ALPS) and B-cell expansion with NF-κB and T-cell anergy (BENTA) syndrome. Increased immature/transitional B cells can be depicted in CBL syndrome, ALPS, and BENTA. Nonetheless, our patients here described showed peculiar B-cell phenotype due to increased immature/transitional CD34<sup>+</sup> B cells. This feature differentiates CBL syndrome from BENTA, pointing toward an abnormal proliferation of B-cell early precursors.</p>