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Updated: Sep 21, 2025
07:38
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
286
Ascorbate Plus Buformin in AML: A Metabolic Targeted Treatment.
Cristina Banella1,2, Gianfranco Catalano1,3, Serena Travaglini1,3
1Neurooncoemtology Units, Santa Lucia Foundation, I.R.C.C.S., 00143 Rome, Italy.
Cancers
|May 28, 2022
Summary
This study reveals that combining ascorbate with buformin effectively targets Acute Myeloid Leukemia (AML) cell metabolism, increasing apoptosis in cancer cells while sparing normal bone marrow progenitors. This combination offers a promising therapeutic strategy for AML treatment.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Acute Myeloid Leukemia (AML) exhibits heterogeneous and flexible metabolic pathways.
- Understanding AML cell metabolism is crucial for developing targeted therapies.
Purpose of the Study:
- To characterize the metabolic profile of AML cells.
- To evaluate the combined efficacy of ascorbate and buformin on AML metabolism and apoptosis.
- To elucidate the mechanism of action of this drug combination.
Main Methods:
- Metabolic analysis of normal hematopoietic progenitors and AML blasts using Seahorse XF Agilent.
- Flow cytometry assays (annexin V, live/dead exclusion) to assess apoptosis.
- Investigation of ascorbate's effect on glycolysis and buformin's impact on mitochondrial respiration.
Main Results:
- Ascorbate inhibits glycolysis by affecting HK1/2 and GLUT1 functions in hematopoietic cells.
- The combination of ascorbate and buformin significantly enhances apoptosis in primary AML blasts.
- This combination reduces mitochondrial respiration and ATP production, downregulates glycolysis, and spares normal CD34+ bone marrow progenitors.
Conclusions:
- The ascorbate-buformin combination demonstrates a potent anti-leukemic effect with a favorable safety profile.
- This therapeutic strategy holds promise for treating refractory/relapsing AML, particularly in fragile patients.
- Further clinical evaluation of ascorbate-buformin in combination therapies for AML is warranted.
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