Donna S. Neuberg

May 8, 2024 | nature.com | Qingyu Luo |Miguel Prado |Xiaowei Wu |Ran Xu |Peter van Galen |John G. Doench | +4 more

AbstractPhosphoinositide-3-kinase-γ (PI3Kγ) is implicated as a target to repolarize tumour-associated macrophages and promote antitumour immune responses in solid cancers1,2,3,4. However, cancer cell-intrinsic roles of PI3Kγ are unclear. Here, by integrating unbiased genome-wide CRISPR interference screening with functional analyses across acute leukaemias, we define a selective dependency on the PI3Kγ complex in a high-risk subset that includes myeloid, lymphoid and dendritic lineages.

Mar 27, 2024 | nature.com | Shai Shimony |Jacqueline Garcia |Marlise R. Luskin |Donna S. Neuberg |Daniel DeAngelo |Richard Stone

AbstractThe clinical impact of molecular ontogeny in acute myeloid leukemia (AML) was defined in patients treated with intensive chemotherapy. In a cohort of 314 newly diagnosed AML patients, we evaluated whether molecular ontogeny subgroups have differential benefit of venetoclax (VEN) added to hypomethylating agents (HMA). In secondary ontogeny (n = 115), median overall survival (OS)(14.1 vs. 6.9 months, P = 0.0054), composite complete remission (cCR 61% vs.

Feb 20, 2024 | nature.com | Shai Shimony |Jan Philipp Bewersdorf |Rory M. Shallis |Guido Marcucci |Daniel DeAngelo |Donna S. Neuberg | +1 more

AbstractMolecularly defined secondary acute myeloid leukemia is associated with a prior myeloid neoplasm and confers a worse prognosis. We compared outcomes of molecularly defined secondary AML patients (n = 395) treated with daunorubicin and cytarabine (7 + 3, n = 167), liposomal daunorubicin and cytarabine (CPX-351, n = 66) or hypomethylating agents (HMA) + venetoclax (VEN) (n = 162). Median overall survival (OS) was comparable between treatment groups among patients aged >60 years.