Decreased Activity of Blood Acid Sphingomyelinase in the Course of Multiple Myeloma

Abstract

Acid sphingomyelinase (aSMase) is involved in the generation of metabolites that function as part of the sphingolipid signaling pathway. It catalyzes the breakdown of sphingomyelin into ceramide, a bioactive lipid that, among other roles, is involved in regulation of apoptosis. Dry drop blood test (DBS) and colorimetric 2-step enzymatic assay were used to assess the activity of human blood aSMase, beta-galactosidase, and beta-glucosidase, these enzymes are lysosomal hydrolases that catalyze the degradation of related sphingolipids, of sphingolipid signaling molecules. Blood was collected from a group of healthy volunteers and patients that were diagnosed with multiple myeloma (MM) in various stages of the disease. Additionally, activity of those enzymes in patients diagnosed with other hematological cancers was also assessed. We found that aSMase activity in the blood of patients with MM (at the time of diagnosis) was 305.43 pmol/spot*20 h, and this value was significantly lower (p < 0.030) compared to the healthy group 441.88 pmol/spot*20 h. Our collected data suggest a possible role of aSMase in pathogenesis of MM development.

Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies

“…Of note and surprisingly, sphingosine, sphinganine, and ceramide levels were found to be higher in AML samples, with a ceramide/S1P ratio significantly higher in AML patient samples compared to control samples [ 187 ]. Similar changes in sphingosine, sphinganine, and ceramide levels were also found in blood samples from patients with multiple myeloma [ 188 ].…”

“…Indeed, exosomes that were high in aSMase were able to confer resistance to cells that were previously responsive to treatment [ 370 ]. However, while analysis of blood samples from multiple myeloma patients showed that ceramide, sphingosine, and sphinganine levels were significantly higher in these patients compared to healthy patients [ 188 ], aSMase activity was significantly lower [ 188 ]. ASMase activation has been also implicated in the induction of cell death by the major polyphenol in green tea extract, EGCG [(−)-epigallocatechin-3-O-gallate] [ 348 , 371 ].…”

“…Moreover, the combination of bortezomib, a proteasome inhibitor and FDA approved drug for multiple myeloma, with inhibition of SPHK2 synergistically increased ER stress and apoptosis [ 114 ]. However, despite the purported functional link between S1P/SPHK2 and survival of multiple myeloma cells, SL analysis of blood samples from 83 multiple myeloma patients at different stages of disease and 17 healthy patients found no difference in S1P levels in multiple myeloma patients compared to healthy patients [ 188 ].…”

Genetic Analysis of Acid β-Glucosidase in Patients with Multiple Myeloma from Central Taiwan: A Small-Cohort Case-Control Study

“…This pathway can contribute to cell growth, division, and survival of cancer cells (Fig. 1) [15, 30, 34-36].…”

Role of Sphingolipids in Multiple Myeloma Progression, Drug Resistance, and Their Potential as Therapeutic Targets

“…These data suggest a possible role for ASM in MM development. Although these results require further analysis and better understanding of their meaning in the context of MM pathogenesis, they point out a possible diagnostic value for ASM levels ( 149 ).…”