Aneuploidy impairs B cell development but accelerates their MYC-driven transformation.

In E μ-Myc transgenic mice, inhibiting apoptosis with BCL2 does not allow CIN-driven aneuploidies to prevail, but high death rates rapidly select viable aneuploid karyotypes.

• Why it matters: CIN can trigger cell death, yet how apoptosis shapes which aneuploid states survive during B cell development and MYC-driven tumorigenesis is unclear.
• What they did: The study impaired the spindle assembly checkpoint by deleting Mitotic Arrest Deficient 2-Like 1 or mutating Monopolar Spindle 1, then used a CRISPR screen to pinpoint mitochondrial apoptosis intermediates and tested them in vivo with B cell–restricted BCL2 overexpression.
• The result: BCL2 overexpression outperformed loss of P53 in vivo, but blocking death was insufficient for aneuploidy-driven transformation; instead, BCL2-regulated apoptosis selected viable aneuploid tumor karyotypes under oncogenic MYC, informing BCL2-targeted therapy implications.

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