Metabolic underpinnings of leukemia pathology and treatment

Abstract

Background Carcinogenic transformation of white blood cells during hematopoiesis leads to the development of leukemia, a cancer characterized by incompetent immune cells and a disruption of normal bone marrow function. Leukemias are diverse in type, affected population, prognosis, and treatment regimen, yet a common theme in leukemia is the dysregulated metabolism of leukemic cells and leukemic stem cells with respect to their noncancerous counterparts. Recent findings In this review, we highlight current findings that elucidate metabolic traits unique to the four major types of leukemia, which confer carcinogenic survival but can be potentially exploited for therapeutic intervention. These metabolic features can work in conjunction with or be independent of unique aspects of the bone marrow microenvironment that can also influence cell survival and proliferation, thus sustaining carcinogenesis. Conclusion Deepening our understanding of the interactions of leukemias with their niche environments in vivo will inform future treatments for leukemia, particularly for those that are refractive to tyrosine kinase inhibitors and other therapeutic mainstays.

Red Blood Cell Metabolic Responses to Torpor and Arousal in the Hibernator Arctic Ground Squirrel

“…57,84 Though devoid of mitochondria, RBCs can uptake, sequester, and metabolize some of these pro inflammatory di/tricarboxylates under hypoxic conditions. 85 Similarly, RBCs can store (via carintine conjugation) and release fatty acids (through active phospholipases and noncanonical redox sensitive lipases such as peroxiredoxin6), a phenomenon that contributes to RBC membrane lipid composition and thus fluidity and deformability. 56 While some free and carnitineconjugated fatty acids increased progressively during torpor-a marker of ongoing lipolysis and fatty acid sequestration inside the RBCs-sudden spikes in polyunsaturated fatty acids and bile acids were noted during middle arousal.…”

The Interplay Between the Genetic and Immune Landscapes of AML: Mechanisms and Implications for Risk Stratification and Therapy

“…Concomitant assessment of leukemia and the immune milieu is accessible via flow cytometry based immunophenotyping (239) while the application of technologies, such as mass cytometry has yet to be incorporated into clinical practice. Metabolic characterization of leukemia and its niche can be performed through metabolomics analysis employing NMR spectroscopy or mass spectrometry or through the measurement of single metabolites of interest (240). Evaluation of the metabolic profile of the leukemic microenvironment could identify actionable metabolic targets ultimately resulting in immunomodulation that complements cytotoxic, targeted or immunotherapy.…”

Druggable Biochemical Pathways and Potential Therapeutic Alternatives to Target Leukemic Stem Cells and Eliminate the Residual Disease in Chronic Myeloid Leukemia

“…LSCs from hematologic disorders establish narrow links with their stroma as a way to regulate their metabolism and redox state which are both crucial for leukemogenesis as described previously [179]. CML cells in their stromal microenvironment express specific metabolic features that represent opportunities for new treatment approaches, some of which are already being tested in clinical trials.…”