scholarly journals Functional Dependency Analysis Identifies Potential Druggable Targets in Acute Myeloid Leukemia

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3710
Author(s):  
Yujia Zhou ◽  
Gregory P. Takacs ◽  
Jatinder K. Lamba ◽  
Christopher Vulpe ◽  
Christopher R. Cogle
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Drug Targets ◽  
Gene Knockout ◽  
Three Dimensional ◽  
Term Survival ◽  
Genome Wide ◽  
Druggable Targets ◽  
Acute Myeloid

Refractory disease is a major challenge in treating patients with acute myeloid leukemia (AML). Whereas the armamentarium has expanded in the past few years for treating AML, long-term survival outcomes have yet to be proven. To further expand the arsenal for treating AML, we searched for druggable gene targets in AML by analyzing screening data from a lentiviral-based genome-wide pooled CRISPR-Cas9 library and gene knockout (KO) dependency scores in 15 AML cell lines (HEL, MV411, OCIAML2, THP1, NOMO1, EOL1, KASUMI1, NB4, OCIAML3, MOLM13, TF1, U937, F36P, AML193, P31FUJ). Ninety-four gene KOs met the criteria of (A) specifically essential to AML cell survival, (B) non-essential in non-AML cells, and (C) druggable according to three-dimensional (3D) modeling or ligand-based druggability scoring. Forty-four of 94 gene-KOs (47%) had an already-approved drug match and comprised a drug development list termed “deKO.” Fifty of 94 gene-KOs (53%) had no drug in development and comprised a drug discovery list termed “disKO.” STRING analysis and gene ontology categorization of the disKO targets preferentially cluster in the metabolic processes of UMP biosynthesis, IMP biosynthesis, dihydrofolate metabolism, pyrimidine nucleobase biosynthesis, vitellogenesis, and regulation of T cell differentiation and hematopoiesis. Results from this study serve as a testable compendium of AML drug targets that, after validation, may be translated into new therapeutics.

Long-term survival after induction therapy with idarubicin and cytosine arabinoside for de novo acute myeloid leukemia

2000 ◽  
Vol 79 (10) ◽  
pp. 533-542 ◽  
Author(s):  
M. Flasshove ◽  
P. Meusers ◽  
J. Schütte ◽  
R. Noppeney ◽  
D. W. Beelen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Therapy ◽  
Cytosine Arabinoside ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Term Survival ◽  
Long Term Survival ◽  
Acute Myeloid

scholarly journals Factors Affecting Long-Term Survival in Acute Myeloid Leukemia

2020 ◽  
pp. 1-2
Author(s):  
Yi-Qian ZHU ◽  
CHEN Bao-An ◽  
Cheng Jian ◽  
Yi-Qian ZHU
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Remission Rate ◽  
Term Survival ◽  
Long Term Survival ◽  
Factors Affecting ◽  
Chemotherapy Drugs ◽  
Common Malignancy ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a common malignancy of the blood system, and most patients are so ill that they often die if they are untreated in time. In recent years, with the improvement of chemotherapy drugs and methods, the complete remission rate has been significantly improved, but the long-term survival rate still has great room for improvement. This review summarized the influencing factors related to the long-term survival of AML patients through reading and sorting out multiple pieces of literature.

scholarly journals Expression of ABCC-Type Nucleotide Exporters in Blasts of Adult Acute Myeloid Leukemia: Relation to Long-term Survival

2009 ◽  
Vol 15 (5) ◽  
pp. 1762-1769 ◽  
Author(s):  
Yanping Guo ◽  
Kathleen Köck ◽  
Christoph A. Ritter ◽  
Zhe-Sheng Chen ◽  
Markus Grube ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Term Survival ◽  
Long Term Survival ◽  
Acute Myeloid

scholarly journals A Rare Case of Coexisting Breast Cancer and Refractory Acute Myeloid Leukemia

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
L. Ballotta ◽  
S. M. Trisolini ◽  
A. P. Iori ◽  
U. La Rocca ◽  
A. Micozzi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Salvage Chemotherapy ◽  
Infectious Complications ◽  
Term Survival ◽  
First Line Therapy ◽  
Refractory Acute Myeloid Leukemia ◽  
Acute Myeloid

The occurrence of acute myeloid leukemia (AML) within six months from a diagnosis of breast cancer (BC) is rarely reported in the literature, and it is associated with a poor prognosis. We report herein the case of a 40-year-old woman referred to our centre affected by BC and simultaneous AML. The patient proved refractory to first line therapy and achieved complete remission (CR) with a clofarabine-based regimen followed by allogeneic stem cell transplantation (ASCT). Both during salvage chemotherapy and after ASCT, the patient presented severe infectious complications ( acute cholecistytis and Nocardia pneumonia, respectively) treated with surgery, and currently she is alive in CR for both diseases after 29 months of follow-up. The case highlights the importance of a diagnostic assessment of any unexplained cytopenia in association with solid neoplasia under treatment, underlining the feasibility and priority of a timely treatment of the haematological neoplasm in order to achieve long-term survival.

Autologous Peripheral Blood Stem Cell Transplantation (PBSCT) Combined with Haploidentical Lymphocytes Infusion Increases the Long Term Survival of Adult Acute Myeloid Leukemia with Standard Risk.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2879-2879
Author(s):  
Bingyi Wu ◽  
Guo Kunyuan ◽  
Haiyan Hu ◽  
Yuliang Yang ◽  
Lan Deng ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Peripheral Blood Stem Cell ◽  
Term Survival ◽  
Standard Risk ◽  
Blood Stem Cell Transplantation ◽  
Acute Myeloid

Abstract OBJECTIVES: The long term survival of adult patients with acute myeloid leukemia with standard risk factor which treated by autologous peripheral blood stem cell transplantation is about 30–50%. We designed a new therapy to improve the long term survival of adult patients with acute myeloid leukemia with standard risk factor. After completely remission, patients underwent 2–3 courses of consolidation chemotherapy. Autologous peripheral blood stem cell transplantation (PBSCT) was performed. After hematology recovery, haploidentical lymphocytes irradiated with 7.5 Gy were infused into patients. Here we evaluate the outcome of this approach in adult patients with acute myeloid leukemia with standard risk. METHODS: From July 1998 to July 2007, twenty-four patients including 17 males and 7 females, median age 36 year old (range 14–58) with acute myeloid leukemia with morphology M2 subtype and normal karotype received this approach therapy. Autologous peripheral blood stem cells were collected by aphereses and froze in −198° and storied after 2–3 courses of median dose cytarabine consolidation chemotherapy The autologous stem cells were grafted to patients following the conditioning with the BuCy regimen (Bu16mg/kg and CTX 120mg/kg). Haploidentical lymphocytes obtained by leukapheresis from sibling donors or other relatives were irradiated with 7.5 Gy and were infused into patients after hematopoietic reconstitution. RESULTS: A median dose of 2.5×108/kg, nucleated cells/kg (range, 2.97×107/kg-6.0×108/kg)containing 5 × 106 CD34+ cells/kg (range,1.5– 4.8) were autografted. All patients were got hematopoietic reconstitution. The median time for granulocyte recovery >0.5 × 109 /L was 11 days and for platelets >20 × 109/L was 14 days following transplantation. All patients were administrated a median dose of 2.0×108/kg haploidentical lymphocytes irradiated with 7.5 Gy. Severe acute GVHD occurred in two patients. One died with severe acute GVHD. Hematopoietic reconstitution delayed in four patients. No other side effects were observed. For the whole group of 24 patients, the median overall survival rate (OSR) was 83.7%. The median disease-free survival (DFS) time was 28.3 moths (range 2–120 m) and the 5-year DFS rate was 50%. The 2-year OS rate was 71%. After a median follow-up of 5.0 years from transplantation, the median DFS and OS were 28.3 years respectively, and the 3-year rates were 50%. Nineteen patients were still in continuous complete remission, 4 patients had relapsed and 3 had died. CONCLUSIONS: Autologous peripheral blood stem cell transplantation (PBSCT) combined with haploidentical lymphocytes infusion may prolong the long term survival of adult acute myeloid leukemia with standard risk.

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