Contributions
Type: Publication Only
Background
The MN1 (Meningioma 1) gene is overexpressed in certain subtypes of acute myeloid leukemia (AML), including patients carrying translocations inv(16)(CBFB-MYH11) and t(8;21)(AML1-ETO) which target the core-binding factor (CBF) transcription factor complex. In consistence, ectopic MN1 expression in mouse bone marrow (BM) cells cultured under myeloid conditions results in increased myeloid colony forming activity and myeloid leukemia. Despite this growing body of evidence describing MN1’s involvement in AML development, it is unknown if MN1 also plays a role in the pathogenesis of lymphoblastic leukemia.
Aims
We aimed to determine expression level of MN1 in pediatric B-ALL as well as effect of ectopic MN1 expression on primary mouse Pro B/pre B-cells in vitro.
Methods
Engogenous MN1 expression in BM samples of 73 pediatric B-ALL patients and healthy controls (n=9), as well as in FACS isolated primary mouse pro B/pre B-cells, were analyzed using RT-qPCR. MN1 was overexpressed in mouse pro B/pre B-cells using retrovirus and followed by methocult assays.
Results
Here we showed that compared with control BM, MN1 expression was increased (2-fold or more) in 29 out of 73 (40%) pediatric B-ALL patient BM. Additional analysis of MN1 expression in sub-groups within our cohort carrying different chromosome translocations showed that carriers of t(12;21)(TEL-AML1) (n=27), targeting CBF, expressed significantly more MN1 than both healthy controls (P=0.02) and the group carrying the t(9;22)(BCR-ABL) (n=9) (P=0.001). In addition, there was a trend of increased MN1 expression in TEL-AML1positive patients (18 out of 27) as compared with patients that are negative for this translocation (n=30). Retroviral MN1 overexpression increased the colony forming activity of mouse Pro B/Pre B cells in vitro.
Summary
Our results suggest that deregulated MN1 expression contributes to the pathogenesis of pediatric B-ALL. Further investigation into the clinical and biological significance of elevated MN1 expression in TEL-AML1positive leukemia might provide insight into additional molecular mechanisms contributing to B-ALL and may lead to improved treatment options for patients.
Keyword(s): ALL, TEL-AML1
Session topic: Publication Only
Type: Publication Only
Background
The MN1 (Meningioma 1) gene is overexpressed in certain subtypes of acute myeloid leukemia (AML), including patients carrying translocations inv(16)(CBFB-MYH11) and t(8;21)(AML1-ETO) which target the core-binding factor (CBF) transcription factor complex. In consistence, ectopic MN1 expression in mouse bone marrow (BM) cells cultured under myeloid conditions results in increased myeloid colony forming activity and myeloid leukemia. Despite this growing body of evidence describing MN1’s involvement in AML development, it is unknown if MN1 also plays a role in the pathogenesis of lymphoblastic leukemia.
Aims
We aimed to determine expression level of MN1 in pediatric B-ALL as well as effect of ectopic MN1 expression on primary mouse Pro B/pre B-cells in vitro.
Methods
Engogenous MN1 expression in BM samples of 73 pediatric B-ALL patients and healthy controls (n=9), as well as in FACS isolated primary mouse pro B/pre B-cells, were analyzed using RT-qPCR. MN1 was overexpressed in mouse pro B/pre B-cells using retrovirus and followed by methocult assays.
Results
Here we showed that compared with control BM, MN1 expression was increased (2-fold or more) in 29 out of 73 (40%) pediatric B-ALL patient BM. Additional analysis of MN1 expression in sub-groups within our cohort carrying different chromosome translocations showed that carriers of t(12;21)(TEL-AML1) (n=27), targeting CBF, expressed significantly more MN1 than both healthy controls (P=0.02) and the group carrying the t(9;22)(BCR-ABL) (n=9) (P=0.001). In addition, there was a trend of increased MN1 expression in TEL-AML1positive patients (18 out of 27) as compared with patients that are negative for this translocation (n=30). Retroviral MN1 overexpression increased the colony forming activity of mouse Pro B/Pre B cells in vitro.
Summary
Our results suggest that deregulated MN1 expression contributes to the pathogenesis of pediatric B-ALL. Further investigation into the clinical and biological significance of elevated MN1 expression in TEL-AML1positive leukemia might provide insight into additional molecular mechanisms contributing to B-ALL and may lead to improved treatment options for patients.
Keyword(s): ALL, TEL-AML1
Session topic: Publication Only