MEIS1 IS ESSENTIAL FOR THE MAINTENANCE OF HUMAN ACUTE MYELOID LEUKEMIA BLASTS INDEPENDENT OF MLL REARRANGEMENTS
(Abstract release date: 05/19/16)
EHA Library. Liu J. 06/09/16; 134545; PB1645
Dr. Jiangying Liu
Contributions
Contributions
Abstract
Abstract: PB1645
Type: Publication Only
Background
Acute myeloid leukemia (AML) is one of the common hematopoietic malignancies with high mortality. Although the outcome of patients with AML has improved by optimized chemotherapy regimens and bone marrow transplantation, leukemia relapse remains one of the most challenging problems during clinical treatment. Sustained existence of AML blasts is a fundamental determinant for the leukemia development and resistance to therapy. Recent evidences suggest that Meis1 is tightly associated with the self-renewal capacity of normal hematopoietic stem cells. Meis1 was also found to be essential for the development of mixed lineage leukemia (MLL)-rearranged leukemia. Whether Meis1 functions independently of MLL abnormality in the context of leukemia is of major interest.
Aims
To elucidate whether Meis1 functions independently of MLL abnormality in the maintenance of leukemia blasts.
Methods
We performed siRNA-mediated gene silencing experiments in the cultured human AML cells without MLL rearrangements. Next, we detected the expression levels of Meis1 in the bone marrows from 95 patients with newly diagnosed AML excluding promyelocytic leukemia and 30 healthy donors. All patients did not express a set of recognized AML-associated fusion genes. The association between the Meis1 levels and the response to chemotherapy was further explored.
Results
Deficiency of Meis1 expression impaired the maintenance and survival of cultured human AML blasts, which is independent of MLL abnormality. In the patients with newly diagnosed AML and without MLL rearrangements, high levels of Meis1 expression were found in 64 of 95 (67.4%) AML patients whereas 31 of 95 (32.6%) patients showed the dramatically low levels, compared with the median level of Meis1 expression in healthy donors. We further demonstrated that high levels of Meis1 expression were associated with the poor response to conventional chemotherapy, compared with the group with low Meis1 levels (p=0.028).
Conclusion
We identified a distinct expression pattern of Meis1 levels in patients with newly diagnosed AML and highlighted a role of Meis1 in regulating maintenance and survival of human AML cells without MLL abnormality. These results implicate Meis1 functions as an important regulator and could be an independent prognostic factor during the progression of human AML.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Maintenance, Meis1, Mixed lineage leukemia
Type: Publication Only
Background
Acute myeloid leukemia (AML) is one of the common hematopoietic malignancies with high mortality. Although the outcome of patients with AML has improved by optimized chemotherapy regimens and bone marrow transplantation, leukemia relapse remains one of the most challenging problems during clinical treatment. Sustained existence of AML blasts is a fundamental determinant for the leukemia development and resistance to therapy. Recent evidences suggest that Meis1 is tightly associated with the self-renewal capacity of normal hematopoietic stem cells. Meis1 was also found to be essential for the development of mixed lineage leukemia (MLL)-rearranged leukemia. Whether Meis1 functions independently of MLL abnormality in the context of leukemia is of major interest.
Aims
To elucidate whether Meis1 functions independently of MLL abnormality in the maintenance of leukemia blasts.
Methods
We performed siRNA-mediated gene silencing experiments in the cultured human AML cells without MLL rearrangements. Next, we detected the expression levels of Meis1 in the bone marrows from 95 patients with newly diagnosed AML excluding promyelocytic leukemia and 30 healthy donors. All patients did not express a set of recognized AML-associated fusion genes. The association between the Meis1 levels and the response to chemotherapy was further explored.
Results
Deficiency of Meis1 expression impaired the maintenance and survival of cultured human AML blasts, which is independent of MLL abnormality. In the patients with newly diagnosed AML and without MLL rearrangements, high levels of Meis1 expression were found in 64 of 95 (67.4%) AML patients whereas 31 of 95 (32.6%) patients showed the dramatically low levels, compared with the median level of Meis1 expression in healthy donors. We further demonstrated that high levels of Meis1 expression were associated with the poor response to conventional chemotherapy, compared with the group with low Meis1 levels (p=0.028).
Conclusion
We identified a distinct expression pattern of Meis1 levels in patients with newly diagnosed AML and highlighted a role of Meis1 in regulating maintenance and survival of human AML cells without MLL abnormality. These results implicate Meis1 functions as an important regulator and could be an independent prognostic factor during the progression of human AML.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Maintenance, Meis1, Mixed lineage leukemia
Abstract: PB1645
Type: Publication Only
Background
Acute myeloid leukemia (AML) is one of the common hematopoietic malignancies with high mortality. Although the outcome of patients with AML has improved by optimized chemotherapy regimens and bone marrow transplantation, leukemia relapse remains one of the most challenging problems during clinical treatment. Sustained existence of AML blasts is a fundamental determinant for the leukemia development and resistance to therapy. Recent evidences suggest that Meis1 is tightly associated with the self-renewal capacity of normal hematopoietic stem cells. Meis1 was also found to be essential for the development of mixed lineage leukemia (MLL)-rearranged leukemia. Whether Meis1 functions independently of MLL abnormality in the context of leukemia is of major interest.
Aims
To elucidate whether Meis1 functions independently of MLL abnormality in the maintenance of leukemia blasts.
Methods
We performed siRNA-mediated gene silencing experiments in the cultured human AML cells without MLL rearrangements. Next, we detected the expression levels of Meis1 in the bone marrows from 95 patients with newly diagnosed AML excluding promyelocytic leukemia and 30 healthy donors. All patients did not express a set of recognized AML-associated fusion genes. The association between the Meis1 levels and the response to chemotherapy was further explored.
Results
Deficiency of Meis1 expression impaired the maintenance and survival of cultured human AML blasts, which is independent of MLL abnormality. In the patients with newly diagnosed AML and without MLL rearrangements, high levels of Meis1 expression were found in 64 of 95 (67.4%) AML patients whereas 31 of 95 (32.6%) patients showed the dramatically low levels, compared with the median level of Meis1 expression in healthy donors. We further demonstrated that high levels of Meis1 expression were associated with the poor response to conventional chemotherapy, compared with the group with low Meis1 levels (p=0.028).
Conclusion
We identified a distinct expression pattern of Meis1 levels in patients with newly diagnosed AML and highlighted a role of Meis1 in regulating maintenance and survival of human AML cells without MLL abnormality. These results implicate Meis1 functions as an important regulator and could be an independent prognostic factor during the progression of human AML.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Maintenance, Meis1, Mixed lineage leukemia
Type: Publication Only
Background
Acute myeloid leukemia (AML) is one of the common hematopoietic malignancies with high mortality. Although the outcome of patients with AML has improved by optimized chemotherapy regimens and bone marrow transplantation, leukemia relapse remains one of the most challenging problems during clinical treatment. Sustained existence of AML blasts is a fundamental determinant for the leukemia development and resistance to therapy. Recent evidences suggest that Meis1 is tightly associated with the self-renewal capacity of normal hematopoietic stem cells. Meis1 was also found to be essential for the development of mixed lineage leukemia (MLL)-rearranged leukemia. Whether Meis1 functions independently of MLL abnormality in the context of leukemia is of major interest.
Aims
To elucidate whether Meis1 functions independently of MLL abnormality in the maintenance of leukemia blasts.
Methods
We performed siRNA-mediated gene silencing experiments in the cultured human AML cells without MLL rearrangements. Next, we detected the expression levels of Meis1 in the bone marrows from 95 patients with newly diagnosed AML excluding promyelocytic leukemia and 30 healthy donors. All patients did not express a set of recognized AML-associated fusion genes. The association between the Meis1 levels and the response to chemotherapy was further explored.
Results
Deficiency of Meis1 expression impaired the maintenance and survival of cultured human AML blasts, which is independent of MLL abnormality. In the patients with newly diagnosed AML and without MLL rearrangements, high levels of Meis1 expression were found in 64 of 95 (67.4%) AML patients whereas 31 of 95 (32.6%) patients showed the dramatically low levels, compared with the median level of Meis1 expression in healthy donors. We further demonstrated that high levels of Meis1 expression were associated with the poor response to conventional chemotherapy, compared with the group with low Meis1 levels (p=0.028).
Conclusion
We identified a distinct expression pattern of Meis1 levels in patients with newly diagnosed AML and highlighted a role of Meis1 in regulating maintenance and survival of human AML cells without MLL abnormality. These results implicate Meis1 functions as an important regulator and could be an independent prognostic factor during the progression of human AML.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Maintenance, Meis1, Mixed lineage leukemia
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