Unexpected profile of sphingolipid contents in blood and bone marrow plasma collected from patients diagnosed with acute myeloid leukemia

TY - JOUR

T1 - Unexpected profile of sphingolipid contents in blood and bone marrow plasma collected from patients diagnosed with acute myeloid leukemia

AU - WAtek, Marzena

AU - Wollny, Tomasz

AU - Pasiarski, Marcin

AU - Gozdz, Stanislaw

AU - Durnas, Bonita

AU - Wolak, Przemyslaw

AU - Bucki, Robert

AU - Marzec, Michal

AU - Chabowska, Anna

AU - Zendzian-Piotrowska, Malgorzata

N1 - M1 - Copyright (C) 2018 U.S. National Library of Medicine. MEDLINE AN 2019291140(Journal; Article; (JOURNAL ARTICLE))

PY - 2017/12/8

Y1 - 2017/12/8

N2 - BACKGROUND: Impaired apoptotic pathways in leukemic cells enable them to grow in an uncontrolled way. Moreover, aberrations in the apoptotic pathways are the main factor of leukemic cells drug resistance.METHODS: To assess the presence of potential abnormalities that might promote dysfunction of leukemic cells growth, HPLC system was used to determine sphingosine (SFO), sphinganine (SFA), sphingosine-1-phosphate (S1P) and ceramide (CER) concentration in the blood collected from patients diagnose with acute myeloblastic leukemia (AML; n = 49) and compare to values of control (healthily) group (n = 51). Additionally, in AML group concentration of SFO, SFA, S1P and CER was determined in bone marrow plasma and compared to respective values in blood plasma. The concentration of S1P and CER binding protein - plasma gelsolin (GSN) was also assessed in collected samples using immunoblotting assay.RESULTS: We observed that in AML patients the average SFO, SFA and CER concentration in blood plasma was significantly higher (p < 0.001) compare to control group, when blood plasma S1P concentration was significantly lower (p < 0.001). At the same time the CER/S1P ratio in AML patient (44.5 ± 19.4) was about 54% higher compare to control group (20.9 ± 13.1). Interestingly the average concentration of S1P in blood plasma (196 ± 13 pmol/ml) was higher compare to its concentration in plasma collected from bone marrow (154 ± 21 pmol/ml).CONCLUSIONS: We hypothesize that changes in profile of sphingolipids concentration and some of their binding protein partners such as GSN in extracellular environment of blood and bone marrow cells in leukemic patients can be targeted to develop new AML treatment method(s).

AB - BACKGROUND: Impaired apoptotic pathways in leukemic cells enable them to grow in an uncontrolled way. Moreover, aberrations in the apoptotic pathways are the main factor of leukemic cells drug resistance.METHODS: To assess the presence of potential abnormalities that might promote dysfunction of leukemic cells growth, HPLC system was used to determine sphingosine (SFO), sphinganine (SFA), sphingosine-1-phosphate (S1P) and ceramide (CER) concentration in the blood collected from patients diagnose with acute myeloblastic leukemia (AML; n = 49) and compare to values of control (healthily) group (n = 51). Additionally, in AML group concentration of SFO, SFA, S1P and CER was determined in bone marrow plasma and compared to respective values in blood plasma. The concentration of S1P and CER binding protein - plasma gelsolin (GSN) was also assessed in collected samples using immunoblotting assay.RESULTS: We observed that in AML patients the average SFO, SFA and CER concentration in blood plasma was significantly higher (p < 0.001) compare to control group, when blood plasma S1P concentration was significantly lower (p < 0.001). At the same time the CER/S1P ratio in AML patient (44.5 ± 19.4) was about 54% higher compare to control group (20.9 ± 13.1). Interestingly the average concentration of S1P in blood plasma (196 ± 13 pmol/ml) was higher compare to its concentration in plasma collected from bone marrow (154 ± 21 pmol/ml).CONCLUSIONS: We hypothesize that changes in profile of sphingolipids concentration and some of their binding protein partners such as GSN in extracellular environment of blood and bone marrow cells in leukemic patients can be targeted to develop new AML treatment method(s).

KW - acute myeloid leukemia

KW - ceramide

KW - hematological malignancies

KW - plasma gelsolin

KW - s1p

KW - sphingolipids

U2 - 10.1186/s12944-017-0624-1

DO - 10.1186/s12944-017-0624-1

M3 - Journal article

C2 - 29216917

SN - 1476-511X

VL - 16

JO - Lipids in Health and Disease

JF - Lipids in Health and Disease

IS - 1

ER -