To determine which niche cell components produce specific SEVs to promote B-ALL development, we generated several tissue-specific Vps33b knockout mice by cross-breeding with Vps33bfl/fl mice with tissue-specific Cre transgenic mice, including Cdh5-Cre (endothelia specific [26]), Prx1-Cre (mesenchymal stem cell specific [27]) and Pf4-Cre (megakaryocyte specific [28]) mice, which can decrease SEV secretion from related niche cells. This evidence concerns the gene VPS33B and precursor B-cell acute lymphoblastic leukemia.