The model for cooperative oncogenesis between Bcl11a and Nf1 deficiency. The thickened lines indicate the major linkage of Bcl11a-Nf1 loss cooperation to leukemogenesis that was identified in this study. The arrows indicate a stimulatory relationship; perpendicular lines, suppression. One major function of Nf1 is to negatively regulate Ras activity, and Nf1 deficiency leads to hyperactivation of Ras.^66,67  Ras activation alone can trigger cell growth arrest and senescence.⁴⁹  However, this effect may be attenuated by an increase in Bcl11a signal, which results in suppression of p21^Cip1 induction and, consequently, release of its control over cell- cycle progression, as discovered in this study. Bcl11a may directly repress Cdkn1a transcription or indirectly through p53 mediated by BCL6^36,68  or SIRT1.^64,65,69