A typical presentation of acute myeloid leukemia

Udayakumar, N; Rajendiran, C; Muthuselvan, R.

doi:10.4103/0973-1482.25858

Cited by 10 publications

(8 citation statements)

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“…Acute myeloid leukemias (AML) are a heterogeneous group of diseases characterized by infiltration of blood, bone marrow, and other tissues by neoplastic cells of the hematopoietic system (Udayakumar et al, 2006). Approximately two-thirds of adults with AML attain complete remission status after induction therapy; however the remission is often not durable, with about 25% of those whom attained complete remission surviving three or more years.…”

Section: Introductionmentioning

confidence: 99%

Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug

He¹,

Tran²,

Gu³

et al. 2017

Drug Metab Dispos

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The absorption, metabolism, and excretion of midostaurin, a potent class III tyrosine protein kinase inhibitor for acute myelogenous leukemia, were evaluated in healthy subjects. A microemulsion formulation was chosen to optimize absorption. After a 50-mg [C]midostaurin dose, oral absorption was high (>90%) and relatively rapid. In plasma, the major circulating components were midostaurin (22%), CGP52421 (32.7%), and CGP62221 (27.7%). Long plasma half-lives were observed for midostaurin (20.3 hours), CGP52421 (495 hours), and CGP62221 (33.4 hours). Through careful mass-balance study design, the recovery achieved was good (81.6%), despite the long radioactivity half-lives. Most of the radioactive dose was recovered in feces (77.6%) mainly as metabolites, because only 3.43% was unchanged, suggesting mainly hepatic metabolism. Renal elimination was minor (4%). Midostaurin metabolism pathways involved hydroxylation, -demethylation, amide hydrolysis, and-demethylation. High plasma CGP52421 and CGP62221 exposures in humans, along with relatively potent cell-based IC for FMS-like tyrosine kinase 3-internal tandem duplications inhibition, suggested that the antileukemic activity in AML patients may also be maintained by the metabolites. Very high plasma protein binding (>99%) required equilibrium gel filtration to identify differences between humans and animals. Because midostaurin, CGP52421, and CGP62221 are metabolized mainly by CYP3A4 and are inhibitors/inducers for CYP3A, potential drug-drug interactions with mainly CYP3A4 modulators/CYP3A substrates could be expected. Given its low aqueous solubility, high oral absorption and extensive metabolism (>90%), midostaurin is a Biopharmaceutics Classification System/Biopharmaceutics Drug Disposition Classification System (BDDCS) class II drug in human, consistent with rat BDDCS in vivo data showing high absorption (>90%) and extensive metabolism (>90%).

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Section: Introductionmentioning

confidence: 99%

Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug

He¹,

Tran²,

Gu³

et al. 2017

Drug Metab Dispos

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“…A literature review found only five patients with AML associated with type B LA ( 5 , 18 – 21 ). Among them, lactate clearance impairment was suspected in three patients because of a history of liver cirrhosis ( 5 ), and a possible liver infiltration by leukemia cells as well as severe renal failure were also found ( 18 , 19 ).…”

Section: Discussionmentioning

confidence: 99%

“…This implies that chemotherapy administration is the main therapeutic action for fast recovery, with the aim of disrupting lactate production by tumor cells ( 1 ). Regression of hyperlactatemia is the general rule and is a good retrospective argument for WE diagnosis ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

The Warburg Effect as a Type B Lactic Acidosis in a Patient With Acute Myeloid Leukemia: A Diagnostic Challenge for Clinicians

Brault¹,

Zerbib²,

Delette³

et al. 2018

Front. Oncol.

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IntroductionThe Warburg effect (WE) is an uncommon cause of type B lactic acidosis (LA) due to a deregulation of carbohydrate metabolism in neoplastic cells where lactic fermentation predominates over oxidative phosphorylation regardless of the oxygen level.Case presentationWe report the case of a 57-year-old man presenting with concomitant acute myeloid leukemia and type B LA with asymptomatic hypoglycemia. We did not find arguments for a septic state, liver dysfunction, or acute mesenteric ischemia. The WE was suspected, and chemotherapy was immediately undertaken. We observed a rapid and sustained decrease in lactate level and normalization of blood glucose. Unfortunately, we noted a relapse of acute leukemia associated with WE soon after treatment initiation and the patient died in the Intensive Care unit.DiscussionSome patients may present complications directly related to an underlying hematological malignancy. The WE is one of these complications and should be suspected in patients with both hypoglycemia and LA. We propose a checklist in order to help clinicians manage this life-threatening complication. Before considering WE, clinicians should eliminate diagnoses such as septic shock or mesenteric ischemia, which require urgent and specific management.ConclusionThe diagnosis of WE can be challenging for clinicians in the Hematology department and the Intensive Care unit. Prompt diagnosis and rapid, adapted chemotherapy initiation may benefit patient survival.

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“…Lactic acidosis has been reported in many leukemia cases (Warburg effect), some of which are mentioned below [ 3 , 25 - 26 ].…”

Section: Reviewmentioning

confidence: 99%

Metabolic Acidosis in Leukemia

Padda¹,

Khalid²,

Kakani³

et al. 2021

Cureus

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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.

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A typical presentation of acute myeloid leukemia

Cited by 10 publications

References 1 publication

Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug

Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug

The Warburg Effect as a Type B Lactic Acidosis in a Patient With Acute Myeloid Leukemia: A Diagnostic Challenge for Clinicians

Metabolic Acidosis in Leukemia

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