科学篇之十五(第2节): The potential of RBM39-Targeted Therapies in AML an

The standard of care (SOC) for Acute Myeloid Leukemia (AML, 急性髓系白血病) and Myelodysplastic Syndromes (MDS, 骨髓增生异常综合征) has evolved over the past decade, incorporating both intensive chemotherapy and targeted therapies, depending on disease subtype, patient age, fitness, and molecular profile.

Chemotherapy ("7+3" regimen):    Cytarabine (7 days) + Anthracycline (3 days)

Targeted therapies: Midostaurin for FLT3-mutated AML (added to 7+3), Gemtuzumab ozogamicin for CD33+ AML (especially favorable-risk cytogenetics), BCL-2 inhibitor Venetoclax, and IDH1/2 inhibitors (Ivosidenib / Enasidenib). 

Limitations of SOC in AML/MDS: 

Issue	Challenge
Short-lived responses	Especially in elderly/unfit or molecularly high-risk subsets
Resistance mechanisms	Particularly with venetoclax, FLT3 inhibitors
High-risk mutations	TP53, ASXL1, splicing factor mutations have poor outcomes
Limited options post-HMA failure	For MDS patients, this remains a major unmet need

RBM39-Targeting May Address: 

Clinical Gap	Impact
HMA-refractory MDS	Median OS <6 months; no approved therapies
Venetoclax resistance in AML	Poor outcomes in R/R elderly AML
Spliceosome-mutant AML/MDS (e.g., SF3B1, SRSF2, U2AF1)	No current splicing-targeted treatments
TP53-mutant disease	Extremely poor prognosis with limited response to SOC
Elderly / unfit patients	Require low-toxicity, outpatient regimens
Secondary / therapy-related AML	Chemoresistant and genetically complex