Vitro Study of Tigecycline to Treat Chronic Myeloid Leukemia

Study Overview
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Brief Summary
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Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm companies with the BCR-ABL fusion gene encoded by the Philadelphia (Ph) chromosome. The BCR-ABL fusion protein(the formation of the chimeric gene BCR/ABL on chromosome 22 and a reciprocal ABL/BCR on chromosome 9,it has no expanded name) plays key role on CML leukemogenesis by activating its downstream signaling pathway of survival and proliferation. Imatinib, a targeted competitive inhibitor of a BCR-ABL tyrosine kinase, changed the clinical treatment and prognosis of CML. As its optimized generation, other tyrosine kinase inhibitors (TKIs), dasatinib and nilotinib have more potent anti-leukemic activity and less side-effect. However, acquired resistance to TKIs is one of the main obstacles to effective CML treatment and is involved in gene amplication of ABL tyrosine kinase point mutations. The outcomes of patients with these ABL tyrosine kinase point mutations have linked to worse prognosis and higher mortality generally. Metabolic adaptations are common in cancer cells, and cancer cells become more dependent on mitochondrial biogenesis. Tigecycline, as a broad-spectrum antibiotics, inhibits mitochondrial biogenesis as its an interesting side-effect.In recent study,researchers indicated that tigecycline can eradicate cancer stem cells by targeting mitochondrial.Here, the investigators test tigecycline's anti-leukemic activity to chronic myeloid leukemia in vitro.

Detailed Description
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In this study, the investigators collected bone marrow(BM) or/and peripheral blood(PB) mononuclear cells from patients with chronic myeloid leukemia.Patients could be in different stages of chronic myeloid leukemia pre-treatment.Additionally, the investigators also selected some healthy volunteers as comparison.Firstly, the investigators analyzed mitochondrial biogenesis and basal metabolic characteristic of mononuclear cells from patients and healthy volunteers.Secondly, the investigators tested the cell viability and apoptosis after tigecycline treatment.Thirdly,the investigators detected the changes of cell mitochondrial biogenesis and metabolic characteristic in the same study sample after tigecycline stimulation. Finally,the investigators analyzed the correlation between sensitivities of mononuclear cells to tigecycline and patients' clinical parameters and survival outcome.

Official Title
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Changes of Mitochondrial Biogenesis and Metabolic Characteristics About Tigecycline to Treat Chronic Myeloid Leukemia in Vitro

Conditions
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Chronic Myeloid Leukemia

Intervention / Treatment
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* Other: blood sampling
* Other: blood sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Philadelphia chromosome positive and/or BCR-ABL positive CML confirmed by cytogenetic and/or molecular analysis; Age >18 years. Eligibility of patients receiving any medications or substances known to affect or determined following review of their case by the Principal Investigator Exclusion Criteria: Patients may not receive any other antibiotics. Patients may not have received prior treatment with TKIs or hydroxyurea. Major cognitive deficits or psychiatric problems hampering a self-reported evaluation. No prior malignancies or any other cancer from which patient has been disease free for 5 years.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with chronic myeloid leukemia<br>100 adult patients(age>18 years),with chronic myeloid leukemia defined by the World Health Organization(WHO) criteria | Other: blood sampling<br>* sampling after diagnosis and the mononuclear cells will be given tigecycline stimulation in vitro<br>|
| Healthy volunteers<br>Healthy volunteers | Other: blood sampling<br>* sampling after register and the mononuclear cells will be given tigecycline stimulation in vitro<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mitochondrial biogenesis and metabolic characteristics of Bone Marrow(BM)/ Peripheral Blood(PB) mononuclear cells |  | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mitochondrial biogenesis and metabolic characteristics of BM/PB mononuclear cells after tigecycline stimulation |  | After Hour 24 and 48 tigecycline stimulation | 
| cell viability and apoptosis of BM/PB mononuclear cells after tigecycline stimulation |  | After Hour 24 and 48 tigecycline stimulation | 
| Patients' clinical characteristics and survival outcomes |  | Through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tigecycline, treatment, mitochondrial biogenesis, metabolic characteristics