Based on our previous observations that incidental conditional CBL deletion in a small fraction of HSCs of CBL-B-null mice, using MMTV-Cre, led to CBL/CBL-B double knockout model with a rapidly-fatal MPD around 8 weeks of age [23], we hypothesized that the prenatal and early neonatal deletion of CBL on a CBL-B-null background using VAV1-Cre could result in a more robust and early CBL/CBL-B DKO in HSCs and produce an early neonatal model of MPD, more closely representative of JMML-associated pathogenic mechanisms. Here, CBLB is linked to myeloproliferative neoplasm.