Contributions
Abstract: PB2080
Type: Publication Only
Background
Oncoprotein kinase Akt (proteinkinase B) plays an important role in the regulation of the cell cycle, apoptosis, glucose metabolism and angiogenesis. There is an opinion that the quantitative level of the Akt kinase phosphoform can be considered as an independent prognostic marker for some types of human malignant neoplasms. Studies of the activated Akt protein are mainly produced in solid tumors. Such studies are few in hematology, but the prognostic and therapeutic prospects make them relevant.
Aims
Study of the level of Akt1 in lysates of bone marrow cells in patients with MDS and an estimation of its prognostic value.
Methods
The level of the activated form of the anti-apoptotic protein Akt1 was analyzed in74 patients with de novo myelodysplastic syndromes (MDS) and 11 with acute myeloid leukemia (AML) as a comparison group. Akt1 in the lysates of bone marrow cells was determined by the EIU the Total-Akt1 DuoSet IC kit (R&D Systems, Inc. USA). The measurements were carried out on an iMark microplate reader (BioRad, Japan). Statistical analysis was made with statistical tools R version 3.1.3.
Results
A high level of the activated form of Akt1 in the lysates of bone marrow cells was established for AML (1428 (103 ... 2319) pg/ml) and for MDS (528.25 (225.9 ... 1788.3) pg/ml) in relation to the control (165.95 (104.5 ... 236.1) pg / ml). In RA, 5q-syndrome and RCMD there was low content of Akt1 compared to RAEB variant: 286.95 (225.9 ... 1788.3) pg/ml for RA and 5q-syndrome, 526.7 (235.8 ... 1765.8) pg/ml with RCMD, 714.3 (235.8 ... 1775.3) pg/ml for RAEB. Analysis of the content of Akt1, depending on the cytogenetic status of bone marrow cells in patients with MDS, showed that the maximum concentration of Akt1 (726.8 (289.6 ... 1316.7) pg/ml) corresponds to multiple karyotype anomalies. The minimum concentration of Akt1 was registered in isolated del 5q31 (286.25 (225.9 ... 289.5) pg/ml). In groups with normal karyotype and isolated chromosomal abnormalities the content of Akt1 in the lysates of bone marrow cells did not differ. Expression of CD95 and FLT3 (CD135) by bone marrow cells has a nonlinear dependence on the level of Akt1. At the Akt1 level in bone marrow cell lysates over 500 pg/ml, the CD95 expression fast falls below 20% and FLT3 (CD135) expression increases by more than 40%. Death of patients with Akt1 content in bone marrow cell lysates more than 500 pg/ml was recorded in 82.5% of cases, and in patients with a concentration of Akt1 less than 500 pg/ml, 44.1% of cases (p <0.001). Transformation to acute leukemia was more frequent with an Akt1 content of more than 500 pg/ml (62.5%) compared to lower values of this parameter (41.2%), p = 0.067. The timing of the onset of MDS transformation into leukemia is statistically significant: 71 (6 ... 340) weeks with Akt1 less than 500 pg/ml and 23.5 (3 ... 133) weeks with Akt1 greater than 500 pg/ml (p <0.001).
Conclusion
An increase in the concentration of the activated form of the Akt1 protein in bone marrow cell lysates corresponds to unfavorable variants of MDS that have a high risk in the IPSS system. The level of Akt1 in bone marrow cell lysates is more than 500 pg/ml and is the threshold for blocking apoptosis and the activity of clonal proliferation. The increased level of the activated form of Akt (more than 500 pg/ml) in the lysates of bone marrow cells can be considered as an independent prognostic marker of the progression of MDS.
Session topic: 9. Myelodysplastic syndromes – Biology & Translational Research
Keyword(s): Akt, Bone Marrow, MDS
Abstract: PB2080
Type: Publication Only
Background
Oncoprotein kinase Akt (proteinkinase B) plays an important role in the regulation of the cell cycle, apoptosis, glucose metabolism and angiogenesis. There is an opinion that the quantitative level of the Akt kinase phosphoform can be considered as an independent prognostic marker for some types of human malignant neoplasms. Studies of the activated Akt protein are mainly produced in solid tumors. Such studies are few in hematology, but the prognostic and therapeutic prospects make them relevant.
Aims
Study of the level of Akt1 in lysates of bone marrow cells in patients with MDS and an estimation of its prognostic value.
Methods
The level of the activated form of the anti-apoptotic protein Akt1 was analyzed in74 patients with de novo myelodysplastic syndromes (MDS) and 11 with acute myeloid leukemia (AML) as a comparison group. Akt1 in the lysates of bone marrow cells was determined by the EIU the Total-Akt1 DuoSet IC kit (R&D Systems, Inc. USA). The measurements were carried out on an iMark microplate reader (BioRad, Japan). Statistical analysis was made with statistical tools R version 3.1.3.
Results
A high level of the activated form of Akt1 in the lysates of bone marrow cells was established for AML (1428 (103 ... 2319) pg/ml) and for MDS (528.25 (225.9 ... 1788.3) pg/ml) in relation to the control (165.95 (104.5 ... 236.1) pg / ml). In RA, 5q-syndrome and RCMD there was low content of Akt1 compared to RAEB variant: 286.95 (225.9 ... 1788.3) pg/ml for RA and 5q-syndrome, 526.7 (235.8 ... 1765.8) pg/ml with RCMD, 714.3 (235.8 ... 1775.3) pg/ml for RAEB. Analysis of the content of Akt1, depending on the cytogenetic status of bone marrow cells in patients with MDS, showed that the maximum concentration of Akt1 (726.8 (289.6 ... 1316.7) pg/ml) corresponds to multiple karyotype anomalies. The minimum concentration of Akt1 was registered in isolated del 5q31 (286.25 (225.9 ... 289.5) pg/ml). In groups with normal karyotype and isolated chromosomal abnormalities the content of Akt1 in the lysates of bone marrow cells did not differ. Expression of CD95 and FLT3 (CD135) by bone marrow cells has a nonlinear dependence on the level of Akt1. At the Akt1 level in bone marrow cell lysates over 500 pg/ml, the CD95 expression fast falls below 20% and FLT3 (CD135) expression increases by more than 40%. Death of patients with Akt1 content in bone marrow cell lysates more than 500 pg/ml was recorded in 82.5% of cases, and in patients with a concentration of Akt1 less than 500 pg/ml, 44.1% of cases (p <0.001). Transformation to acute leukemia was more frequent with an Akt1 content of more than 500 pg/ml (62.5%) compared to lower values of this parameter (41.2%), p = 0.067. The timing of the onset of MDS transformation into leukemia is statistically significant: 71 (6 ... 340) weeks with Akt1 less than 500 pg/ml and 23.5 (3 ... 133) weeks with Akt1 greater than 500 pg/ml (p <0.001).
Conclusion
An increase in the concentration of the activated form of the Akt1 protein in bone marrow cell lysates corresponds to unfavorable variants of MDS that have a high risk in the IPSS system. The level of Akt1 in bone marrow cell lysates is more than 500 pg/ml and is the threshold for blocking apoptosis and the activity of clonal proliferation. The increased level of the activated form of Akt (more than 500 pg/ml) in the lysates of bone marrow cells can be considered as an independent prognostic marker of the progression of MDS.
Session topic: 9. Myelodysplastic syndromes – Biology & Translational Research
Keyword(s): Akt, Bone Marrow, MDS