ASSESSMENT OF BAALC AND MN1 GENE EXPRESSION LEVEL COULD CONTRIBUTE TO IMPROVED PROGNOSTIC STRATIFICATION OF THE AML-NK PATIENTS
(Abstract release date: 05/19/16)
EHA Library. Marjanovic I. 06/09/16; 132481; E932
Mrs. Irena Marjanovic
Contributions
Contributions
Abstract
Abstract: E932
Type: Eposter Presentation
Background
There is a constant need for the introduction of new molecular markers in AML-NK group of patients in order to ensure more precise risk stratification. The latest attempt was the inclusion of expression level changes of some genes, like BAALC (brain and acute leukemia, cytoplasmic) and MN1 (meningioma 1). MN1 is an oncoprotein found to function as transcription coactivator, while the BAALC function is not yet clearly defined. Both of the genes are highly expressed in hematopoietic progenitor cells and are down-regulated during differentiation.
Aims
Aim of this study was to evaluate the BAALC and MN1 gene expression levels in de novo AML-NK patients, and to investigate association with other molecular and clinical data.
Methods
Fresh bone marrow (BM) samples were collected from 111 AML-NK patients at diagnosis (62 male, 49 female, median age 54 years, range 19-78). Relative quantification analysis of BAALC and MN1 expression level was performed by RQ-PCR methodology, using comparative ddCt method with healthy controls as calibrator.
Results
The median expression level of BAALC and MN1 among patients was 1.55 (0.01–4246.00) and 1.59 (0.00–67.74), while the levels detected among healthy controls was 1.00 (0.65–3.63) and 1.00 (0.40–2.53), respectively. The existence of a positive correlation between BAALC and MN1 expression was detected (r=0.693). Using median value of gene expression levels among healthy individuals plus 3xSD as a cut-off value, we found that 42 patients (38%) expressed BAALC gene, while 43 patients (39%) expressed MN1. Neither BAALC+ nor MN1+ status, had any association with usual clinical characteristics. The BAALC+/ MN1+ status was not associated with the presence of FLT3 and IDH1/IDH2 mutations, but exhibited strong correlation with NPM1wt status (p<0.001). Only 2/42 BAALC+ and 2/43 MN1+ patients were found to have NPM1 mutations.When among BAALC+ and MN1+ patients median expression level of adequate gene was introduced as a cut-off value, patients were divided into BAALChigh/BAALClow (21/21) and MN1high/MN1low (21/22) patients. NPM1 mutations could not be found in none of the high expressing group of patients (BAALChigh or MN1high), FLT3-ITD could be detected in only four patients, and therefore the most frequent were the patients with so called FLT3-ITD/NPM1 double negative status. Compared to MN1low group, MN1high patients tend to have lover CR rate (41% vs. 59%; p=0.227), and it was confirmed in the survival analyses where MN1high patients had lower DFS (12 months vs. 30 months; p=0.319) and also shorter OS (5 months vs. 20 months; p=0.069). Similar findings were detected for BAALChigh patients who, in comparison with BAALClow patients, had a tendency to lower CR (42% vs. 58%) and resistant disease (67% vs. 33%). In survival analyses BAALChigh patients had lower DFS (12 months vs. 18 months; p=0.261) and OS (5 months vs. 8 months; p=0.196).
Conclusion
In our cohort of AML-NK patients, overexpression of either BAALC or MN1 is a factor of poor prognosis. This finding could especially contribute to an improved risk stratification among FLT3-ITD/NPM1 double negative patients lacking a reliable prognostic marker.
Session topic: E-poster
Type: Eposter Presentation
Background
There is a constant need for the introduction of new molecular markers in AML-NK group of patients in order to ensure more precise risk stratification. The latest attempt was the inclusion of expression level changes of some genes, like BAALC (brain and acute leukemia, cytoplasmic) and MN1 (meningioma 1). MN1 is an oncoprotein found to function as transcription coactivator, while the BAALC function is not yet clearly defined. Both of the genes are highly expressed in hematopoietic progenitor cells and are down-regulated during differentiation.
Aims
Aim of this study was to evaluate the BAALC and MN1 gene expression levels in de novo AML-NK patients, and to investigate association with other molecular and clinical data.
Methods
Fresh bone marrow (BM) samples were collected from 111 AML-NK patients at diagnosis (62 male, 49 female, median age 54 years, range 19-78). Relative quantification analysis of BAALC and MN1 expression level was performed by RQ-PCR methodology, using comparative ddCt method with healthy controls as calibrator.
Results
The median expression level of BAALC and MN1 among patients was 1.55 (0.01–4246.00) and 1.59 (0.00–67.74), while the levels detected among healthy controls was 1.00 (0.65–3.63) and 1.00 (0.40–2.53), respectively. The existence of a positive correlation between BAALC and MN1 expression was detected (r=0.693). Using median value of gene expression levels among healthy individuals plus 3xSD as a cut-off value, we found that 42 patients (38%) expressed BAALC gene, while 43 patients (39%) expressed MN1. Neither BAALC+ nor MN1+ status, had any association with usual clinical characteristics. The BAALC+/ MN1+ status was not associated with the presence of FLT3 and IDH1/IDH2 mutations, but exhibited strong correlation with NPM1wt status (p<0.001). Only 2/42 BAALC+ and 2/43 MN1+ patients were found to have NPM1 mutations.When among BAALC+ and MN1+ patients median expression level of adequate gene was introduced as a cut-off value, patients were divided into BAALChigh/BAALClow (21/21) and MN1high/MN1low (21/22) patients. NPM1 mutations could not be found in none of the high expressing group of patients (BAALChigh or MN1high), FLT3-ITD could be detected in only four patients, and therefore the most frequent were the patients with so called FLT3-ITD/NPM1 double negative status. Compared to MN1low group, MN1high patients tend to have lover CR rate (41% vs. 59%; p=0.227), and it was confirmed in the survival analyses where MN1high patients had lower DFS (12 months vs. 30 months; p=0.319) and also shorter OS (5 months vs. 20 months; p=0.069). Similar findings were detected for BAALChigh patients who, in comparison with BAALClow patients, had a tendency to lower CR (42% vs. 58%) and resistant disease (67% vs. 33%). In survival analyses BAALChigh patients had lower DFS (12 months vs. 18 months; p=0.261) and OS (5 months vs. 8 months; p=0.196).
Conclusion
In our cohort of AML-NK patients, overexpression of either BAALC or MN1 is a factor of poor prognosis. This finding could especially contribute to an improved risk stratification among FLT3-ITD/NPM1 double negative patients lacking a reliable prognostic marker.
Session topic: E-poster
Abstract: E932
Type: Eposter Presentation
Background
There is a constant need for the introduction of new molecular markers in AML-NK group of patients in order to ensure more precise risk stratification. The latest attempt was the inclusion of expression level changes of some genes, like BAALC (brain and acute leukemia, cytoplasmic) and MN1 (meningioma 1). MN1 is an oncoprotein found to function as transcription coactivator, while the BAALC function is not yet clearly defined. Both of the genes are highly expressed in hematopoietic progenitor cells and are down-regulated during differentiation.
Aims
Aim of this study was to evaluate the BAALC and MN1 gene expression levels in de novo AML-NK patients, and to investigate association with other molecular and clinical data.
Methods
Fresh bone marrow (BM) samples were collected from 111 AML-NK patients at diagnosis (62 male, 49 female, median age 54 years, range 19-78). Relative quantification analysis of BAALC and MN1 expression level was performed by RQ-PCR methodology, using comparative ddCt method with healthy controls as calibrator.
Results
The median expression level of BAALC and MN1 among patients was 1.55 (0.01–4246.00) and 1.59 (0.00–67.74), while the levels detected among healthy controls was 1.00 (0.65–3.63) and 1.00 (0.40–2.53), respectively. The existence of a positive correlation between BAALC and MN1 expression was detected (r=0.693). Using median value of gene expression levels among healthy individuals plus 3xSD as a cut-off value, we found that 42 patients (38%) expressed BAALC gene, while 43 patients (39%) expressed MN1. Neither BAALC+ nor MN1+ status, had any association with usual clinical characteristics. The BAALC+/ MN1+ status was not associated with the presence of FLT3 and IDH1/IDH2 mutations, but exhibited strong correlation with NPM1wt status (p<0.001). Only 2/42 BAALC+ and 2/43 MN1+ patients were found to have NPM1 mutations.When among BAALC+ and MN1+ patients median expression level of adequate gene was introduced as a cut-off value, patients were divided into BAALChigh/BAALClow (21/21) and MN1high/MN1low (21/22) patients. NPM1 mutations could not be found in none of the high expressing group of patients (BAALChigh or MN1high), FLT3-ITD could be detected in only four patients, and therefore the most frequent were the patients with so called FLT3-ITD/NPM1 double negative status. Compared to MN1low group, MN1high patients tend to have lover CR rate (41% vs. 59%; p=0.227), and it was confirmed in the survival analyses where MN1high patients had lower DFS (12 months vs. 30 months; p=0.319) and also shorter OS (5 months vs. 20 months; p=0.069). Similar findings were detected for BAALChigh patients who, in comparison with BAALClow patients, had a tendency to lower CR (42% vs. 58%) and resistant disease (67% vs. 33%). In survival analyses BAALChigh patients had lower DFS (12 months vs. 18 months; p=0.261) and OS (5 months vs. 8 months; p=0.196).
Conclusion
In our cohort of AML-NK patients, overexpression of either BAALC or MN1 is a factor of poor prognosis. This finding could especially contribute to an improved risk stratification among FLT3-ITD/NPM1 double negative patients lacking a reliable prognostic marker.
Session topic: E-poster
Type: Eposter Presentation
Background
There is a constant need for the introduction of new molecular markers in AML-NK group of patients in order to ensure more precise risk stratification. The latest attempt was the inclusion of expression level changes of some genes, like BAALC (brain and acute leukemia, cytoplasmic) and MN1 (meningioma 1). MN1 is an oncoprotein found to function as transcription coactivator, while the BAALC function is not yet clearly defined. Both of the genes are highly expressed in hematopoietic progenitor cells and are down-regulated during differentiation.
Aims
Aim of this study was to evaluate the BAALC and MN1 gene expression levels in de novo AML-NK patients, and to investigate association with other molecular and clinical data.
Methods
Fresh bone marrow (BM) samples were collected from 111 AML-NK patients at diagnosis (62 male, 49 female, median age 54 years, range 19-78). Relative quantification analysis of BAALC and MN1 expression level was performed by RQ-PCR methodology, using comparative ddCt method with healthy controls as calibrator.
Results
The median expression level of BAALC and MN1 among patients was 1.55 (0.01–4246.00) and 1.59 (0.00–67.74), while the levels detected among healthy controls was 1.00 (0.65–3.63) and 1.00 (0.40–2.53), respectively. The existence of a positive correlation between BAALC and MN1 expression was detected (r=0.693). Using median value of gene expression levels among healthy individuals plus 3xSD as a cut-off value, we found that 42 patients (38%) expressed BAALC gene, while 43 patients (39%) expressed MN1. Neither BAALC+ nor MN1+ status, had any association with usual clinical characteristics. The BAALC+/ MN1+ status was not associated with the presence of FLT3 and IDH1/IDH2 mutations, but exhibited strong correlation with NPM1wt status (p<0.001). Only 2/42 BAALC+ and 2/43 MN1+ patients were found to have NPM1 mutations.When among BAALC+ and MN1+ patients median expression level of adequate gene was introduced as a cut-off value, patients were divided into BAALChigh/BAALClow (21/21) and MN1high/MN1low (21/22) patients. NPM1 mutations could not be found in none of the high expressing group of patients (BAALChigh or MN1high), FLT3-ITD could be detected in only four patients, and therefore the most frequent were the patients with so called FLT3-ITD/NPM1 double negative status. Compared to MN1low group, MN1high patients tend to have lover CR rate (41% vs. 59%; p=0.227), and it was confirmed in the survival analyses where MN1high patients had lower DFS (12 months vs. 30 months; p=0.319) and also shorter OS (5 months vs. 20 months; p=0.069). Similar findings were detected for BAALChigh patients who, in comparison with BAALClow patients, had a tendency to lower CR (42% vs. 58%) and resistant disease (67% vs. 33%). In survival analyses BAALChigh patients had lower DFS (12 months vs. 18 months; p=0.261) and OS (5 months vs. 8 months; p=0.196).
Conclusion
In our cohort of AML-NK patients, overexpression of either BAALC or MN1 is a factor of poor prognosis. This finding could especially contribute to an improved risk stratification among FLT3-ITD/NPM1 double negative patients lacking a reliable prognostic marker.
Session topic: E-poster
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