The Ikaros gene is required for normal development of lymphocytes and frequent intragenic deletions of Ikaros have been identified in acute lymphoblastic leukemia.However,little is known about the role of Ikaros in my...The Ikaros gene is required for normal development of lymphocytes and frequent intragenic deletions of Ikaros have been identified in acute lymphoblastic leukemia.However,little is known about the role of Ikaros in myeloid malignancies.Here we discuss the role of Ikaros as a lineage master regulator during the onset and progression of myeloid leukemias,namely CALM-AF10 positive acute myeloid leukemia and chronic myeloid leukemia.Alterations of Ikaros at the gene or protein level may act as a bi-directional lineage switch subverting developmental plasticity for malignant transformation.Finally,we propose that promiscuous signaling involving Ikaros and FOXO transcription factors might be a critical link between early lineage fate and uncontrolled proliferation.展开更多
Objectives: To define the involvement of CALM and AF10 fusion transcripts in primary leukaemias with t(10; 11). Methods: The AF10 and CALM fusion in five t(10; 11) leukemia samples were checked by reverse transcriptas...Objectives: To define the involvement of CALM and AF10 fusion transcripts in primary leukaemias with t(10; 11). Methods: The AF10 and CALM fusion in five t(10; 11) leukemia samples were checked by reverse transcriptase-polymerase chain reaction (RT-PCR), and effects of CALM/AF10 antisense phosphorothioate oligodeoxynucleotides (AS PS-ODNs) on chemotherapy sensitivity and apoptosis of leukemia cells in vitro were observed. Results: Five different-sized AF10-CALM products and four different-sized CALM/AF10 products were detected by RT-PCR. The chemotherapy sensitivity of leukemic cells with t(10; 11) to drugs in vitro was lower than that of leukemic cells without t(10; 11). AS PS-ODNs increased the chemotherapy sensitivity and apoptotic rate. There were 4 cases positive at 5 μmol/L concentration, all cases positive at 10 μmol/L and 20 μmol/L concentration, P<0.01 vs only chemotherapeutic drugs (3 cases positive), and chemotherapeutic drugs + S-PS-ODNs (10 μmol/L) (3 cases positive). After cells were treated with 10 μmol/L AS-PS-ODNs + chemotherapeutic drugs for 48 h, 72 h, 96 h, the apoptotic indexes were 14.22±2.86, 29.39±3.57, and 41.26±4.52, respectively. These were significantly higher than those of only chemotherapeutic drugs-treated cells and chemotherapeutic drugs + S-PS-ODNs-treated cells at corresponding time (P<0.01). There was no difference between only drugs group and S-PS-ODNs group at corresponding time (P>0.05). Conclusion: The CALM and AF10 fusion transcripts are involved in the pathogenesis of haematological malignancies with t(10, 11), and is associated with a poor prognosis. AS-PS-ODNs might be useful in therapy of t(10, 11) leukemia. Key words AF10 - CALM - Fusion transcript - Primary leukemia cell - In vitro sensitivity - Antisense oligodeoxynucleotide CLC number R733.7 Biography: LIU Ge-xiu (1968–), male, associate professor, Institute of Hematology, Medical College, Jinan University, majors in hematology.展开更多
文摘The Ikaros gene is required for normal development of lymphocytes and frequent intragenic deletions of Ikaros have been identified in acute lymphoblastic leukemia.However,little is known about the role of Ikaros in myeloid malignancies.Here we discuss the role of Ikaros as a lineage master regulator during the onset and progression of myeloid leukemias,namely CALM-AF10 positive acute myeloid leukemia and chronic myeloid leukemia.Alterations of Ikaros at the gene or protein level may act as a bi-directional lineage switch subverting developmental plasticity for malignant transformation.Finally,we propose that promiscuous signaling involving Ikaros and FOXO transcription factors might be a critical link between early lineage fate and uncontrolled proliferation.
文摘Objectives: To define the involvement of CALM and AF10 fusion transcripts in primary leukaemias with t(10; 11). Methods: The AF10 and CALM fusion in five t(10; 11) leukemia samples were checked by reverse transcriptase-polymerase chain reaction (RT-PCR), and effects of CALM/AF10 antisense phosphorothioate oligodeoxynucleotides (AS PS-ODNs) on chemotherapy sensitivity and apoptosis of leukemia cells in vitro were observed. Results: Five different-sized AF10-CALM products and four different-sized CALM/AF10 products were detected by RT-PCR. The chemotherapy sensitivity of leukemic cells with t(10; 11) to drugs in vitro was lower than that of leukemic cells without t(10; 11). AS PS-ODNs increased the chemotherapy sensitivity and apoptotic rate. There were 4 cases positive at 5 μmol/L concentration, all cases positive at 10 μmol/L and 20 μmol/L concentration, P<0.01 vs only chemotherapeutic drugs (3 cases positive), and chemotherapeutic drugs + S-PS-ODNs (10 μmol/L) (3 cases positive). After cells were treated with 10 μmol/L AS-PS-ODNs + chemotherapeutic drugs for 48 h, 72 h, 96 h, the apoptotic indexes were 14.22±2.86, 29.39±3.57, and 41.26±4.52, respectively. These were significantly higher than those of only chemotherapeutic drugs-treated cells and chemotherapeutic drugs + S-PS-ODNs-treated cells at corresponding time (P<0.01). There was no difference between only drugs group and S-PS-ODNs group at corresponding time (P>0.05). Conclusion: The CALM and AF10 fusion transcripts are involved in the pathogenesis of haematological malignancies with t(10, 11), and is associated with a poor prognosis. AS-PS-ODNs might be useful in therapy of t(10, 11) leukemia. Key words AF10 - CALM - Fusion transcript - Primary leukemia cell - In vitro sensitivity - Antisense oligodeoxynucleotide CLC number R733.7 Biography: LIU Ge-xiu (1968–), male, associate professor, Institute of Hematology, Medical College, Jinan University, majors in hematology.
