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Cancer cells rely on altered metabolism to support abnormal proliferation. We performed a CRISPR/Cas9 functional genomic screen targeting metabolic enzymes and identified PDXK-an enzyme that produces pyridoxal phosphate (PLP) from vitamin B6-as an acute myeloid leukemia (AML)-selective dependency. PDXK kinase activity is required for PLP production and AML cell proliferation, and pharmacological blockade of the vitamin B6 pathway at both PDXK and PLP levels recapitulated PDXK disruption effects. PDXK disruption reduced intracellular concentrations of key metabolites needed for cell division. Furthermore, disruption of PLP-dependent enzymes ODC1 or GOT2 selectively inhibited AML cell proliferation and their downstream products partially rescued PDXK disruption induced proliferation blockage. Our work identifies the vitamin B6 pathway as a pharmacologically actionable dependency in AML.
This article was published in the following journal.
Name: Cancer cell
Vitamin D (VD) is a known differentiating agent, but the role of VD receptor (VDR) is still incompletely described in acute myeloid leukemia (AML), whose treatment is based mostly on antimitotic chemo...
To provide a comprehensive review of evidence-based data on the newly approved therapeutic agents in acute myeloid leukemia (AML) with regards to appropriate indications for use, efficacy, and safety.
Identification of cytogenetic and molecular abnormalities has become vital for the appropriate treatment of acute myeloid leukemia (AML). One of the most common molecular alterations in AML is the con...
To review the current state of molecular and genetic profiling of acute myeloid leukemia (AML) and its implications.
Myelodysplastic syndrome (MDS) that evolves into acute leukemia with blasts of mixed phenotypes has rarely been reported and has no distinct diagnostic category. Herein, we describe a 79-year-old Kore...
Acute myeloid leukemia (AML) is a group of genetically highly heterogeneous malignant disease . The disease is the most common type of adult acute leukemia. Overall survival (OS) was less ...
This research trial studies metabolic changes in blood samples from patients with acute myeloid leukemia. Studying samples of blood from patients with acute myeloid leukemia in the laborat...
A Phase I/IIa, open-label, uncontrolled study to evaluate the safety and efficacy of Astarabine (BST-236) as single agent in patients with refractory or relapsed Acute Myeloid Leukemia (AM...
RATIONALE: Vaccines made from peptides that are found on leukemia cells may make the body build an immune response and kill cancer cells. Combining vaccine therapy with the immune adjuvant...
RATIONALE: Diagnostic procedures, such as genetic testing, may improve the ability to detect acute myeloid leukemia and determine the extent of disease. PURPOSE: Diagnostic study to try t...
A pediatric acute myeloid leukemia involving both myeloid and monocytoid precursors. At least 20% of non-erythroid cells are of monocytic origin.
A rare acute myeloid leukemia characterized by abnormal EOSINOPHILS in the bone marrow.
An acute myeloid leukemia in which abnormal PROMYELOCYTES predominate. It is frequently associated with DISSEMINATED INTRAVASCULAR COAGULATION.
An acute leukemia exhibiting cell features characteristic of both the myeloid and lymphoid lineages and probably arising from MULTIPOTENT STEM CELLS.
Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...
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