Metabolic Acidosis in Leukemia.

Jaskamal Padda,Gutteridge Jean-Charles,Varsha Kakani,Ayden Charlene Cooper,Khizer Khalid

doi:10.7759/cureus.17732

Abstract

In 2020, the incidence of leukemia was 474,519 with 311,594 mortality worldwide. In 2021, the American Cancer Society (ACS) has estimated 61,090 new cases of leukemia to occur within the United States. It has also been reported that the most common cause of death in children from one to fourteen years old is oncological, with leukemia being the most frequent cause. A phenomenon known as the Warburg effect has been affiliated with cancer. The Warburg effect is a metabolic abnormality of lactic acidosis in malignancies, with most cases presenting as hematological malignancies such as leukemia. Although many theories have been formulated to clarify the role of the Warburg effect, the exact role still remains uncertain. Four suggested theories on why the Warburg effect happens to include cell signaling, adenosine triphosphate (ATP) synthesis, biosynthesis, and the tumor microenvironment. The Warburg effect occurs in leukemia with the help of enzymes such as pyruvate kinases M2 (PKM2), lactate dehydrogenase A (LDHA), pyruvate dehydrogenase kinase 1 (PDK1), and fibroblast growth factor receptor 1 (FGFR1). In this literature, we explain the proposed hypotheses of the Warburg effect, along with the molecular mechanism of how leukemia is able to produce lactic acid, with the intent to better understand this phenomenon.

Highlights

BackgroundIn 2020, 474,519 new cases of leukemia with 311,594 deaths were recorded globally
Type B lactic acidosis is a form of metabolic acidosis which is a complication in leukemia
The Warburg effect was discovered in 1925 by Warburg O, who observed an increase in lactic acid production in neoplastic cells, with most occurring in hematological malignancies such as leukemia

Summary

Introduction

In 2020, 474,519 new cases of leukemia with 311,594 deaths were recorded globally. Out of the 474,519 cases, 269,503 of them were males and 205,016 leukemia cases were in females [1]. The theorized mechanism by which these events occur is by increasing lactic acid production via aerobic glycolysis, causing hydrogen to disperse from the tumor microenvironment into the neighboring normal tissues This leads to the remodeling of cells and permitting local tissue invasion [18, 19]. A study done by Bonnet showed that inhibition of pyruvate dehydrogenase kinase can revert aerobic glycolysis back to oxidative phosphorylation, further inhibiting tumor growth and decreasing lactic acid levels [24]. Patients presenting with lactic acidosis without clinical evidence of tissue hypoperfusion should raise the question of an underlying malignancy, hematological disorders, or leukemia relapse This should prompt further testing to establish the diagnosis of which type of leukemia it is with complete blood count and bone marrow biopsy [27]. Further research is required for the use of thiamine replacement therapy in the treatment of metabolic acidosis in leukemia. [27, 29]

Conclusions

Disclosures