Summary： Patients with FLT3-ITD^mmutt/NPM1- cytogenetically normal acute myeloid leukemia （CN-AML）, as high-risk molecular group in CN-AML, are associated with a worse prognosis than other CN-AML patients. It is be...Summary： Patients with FLT3-ITD^mmutt/NPM1- cytogenetically normal acute myeloid leukemia （CN-AML）, as high-risk molecular group in CN-AML, are associated with a worse prognosis than other CN-AML patients. It is beneficial to generate xenotransplantation model of FLT3-ITD^mut/NPM1- CN-AML to better understand the pathogenesis and therapeutic strategies of such AML subtype. The purpose of present study was to establish the xenotransplantation model in NOD/SCID mice with FLT3-ITD^mut/NPM1- CN-AML primary cells. The FLT3-ITD^mut/NPM1- CN-AML primary cells from 3 of 7 cases were successfully transplanted into NOD/SCID mice, and human CD45 positive cells were detected in the peripheral blood, spleen and bone marrow of mice by using flow cytometry. Infiltration of human leukemia cells in various organs of mice was observed by using immunohistochemistry. Gene analysis confirmed sustained FLT3/ITD mutation without NPM1 mutation in mice. By performing serial transplantation, it was found that characteristics of the leukemia cells in secondary and tertiary genera- tion models remained unchanged. Moreover, in vivo cytarabine administration could extend survival of NOD/SCID mice, which was consistent with clinical observation. In conclusion, we successfully estab- lished xenotransplantation model of human FLT3-ITD^mut/NPM1- CN-AML in NOD/SCID mice. The model was able to present primary disease and suitable to evaluate the curative effects of new drugs or therapy strategies.展开更多
BACKGROUND Acute myeloid leukemia is often associated with gene mutation or chromosome abnormality,which is an important factor affecting prognosis.The 5-year survival rate of patients with acute myeloid leukemia with...BACKGROUND Acute myeloid leukemia is often associated with gene mutation or chromosome abnormality,which is an important factor affecting prognosis.The 5-year survival rate of patients with acute myeloid leukemia without hematopoietic stem cell transplantation is low.For patients who only received chemotherapy and whose first remission lasted>5 years,there are few reports of gene spectrum changes between relapse and initial diagnosis.CASE SUMMARY We report a 41-year-old woman who presented to our hospital with complaints of dizziness,poor appetite and wasting.She was diagnosed with acute myelomonocytic leukemia(M4b)with NPM1 mutation and only received chemotherapy.Her first remission lasted>5 years.New genetic variants were detected upon relapse that may have been related to relapse and chemotherapy resistance.CONCLUSION Mutations in WT1(R394fs/A387fs)/PTPN11 T73I/ETV6 S350P and JAK2 W659R may be related to relapse and chemotherapy resistance in acute myeloid leukemia.展开更多
基金supported by the National Natural Science Foundation of China (No. 81200380)
文摘Summary： Patients with FLT3-ITD^mmutt/NPM1- cytogenetically normal acute myeloid leukemia （CN-AML）, as high-risk molecular group in CN-AML, are associated with a worse prognosis than other CN-AML patients. It is beneficial to generate xenotransplantation model of FLT3-ITD^mut/NPM1- CN-AML to better understand the pathogenesis and therapeutic strategies of such AML subtype. The purpose of present study was to establish the xenotransplantation model in NOD/SCID mice with FLT3-ITD^mut/NPM1- CN-AML primary cells. The FLT3-ITD^mut/NPM1- CN-AML primary cells from 3 of 7 cases were successfully transplanted into NOD/SCID mice, and human CD45 positive cells were detected in the peripheral blood, spleen and bone marrow of mice by using flow cytometry. Infiltration of human leukemia cells in various organs of mice was observed by using immunohistochemistry. Gene analysis confirmed sustained FLT3/ITD mutation without NPM1 mutation in mice. By performing serial transplantation, it was found that characteristics of the leukemia cells in secondary and tertiary genera- tion models remained unchanged. Moreover, in vivo cytarabine administration could extend survival of NOD/SCID mice, which was consistent with clinical observation. In conclusion, we successfully estab- lished xenotransplantation model of human FLT3-ITD^mut/NPM1- CN-AML in NOD/SCID mice. The model was able to present primary disease and suitable to evaluate the curative effects of new drugs or therapy strategies.
基金the Shantou Science and Technology Planning Project of Guangdong Province,No.SFK[2019]79.
文摘BACKGROUND Acute myeloid leukemia is often associated with gene mutation or chromosome abnormality,which is an important factor affecting prognosis.The 5-year survival rate of patients with acute myeloid leukemia without hematopoietic stem cell transplantation is low.For patients who only received chemotherapy and whose first remission lasted>5 years,there are few reports of gene spectrum changes between relapse and initial diagnosis.CASE SUMMARY We report a 41-year-old woman who presented to our hospital with complaints of dizziness,poor appetite and wasting.She was diagnosed with acute myelomonocytic leukemia(M4b)with NPM1 mutation and only received chemotherapy.Her first remission lasted>5 years.New genetic variants were detected upon relapse that may have been related to relapse and chemotherapy resistance.CONCLUSION Mutations in WT1(R394fs/A387fs)/PTPN11 T73I/ETV6 S350P and JAK2 W659R may be related to relapse and chemotherapy resistance in acute myeloid leukemia.
