Genomics of primary chemoresistance and remission induction failure in paediatric and adult acute myeloid leukaemia.
نویسندگان
چکیده
Cure rates of children and adults with acute myeloid leukaemia (AML) remain unsatisfactory partly due to chemotherapy resistance. We investigated the genetic basis of AML in 107 primary cases by sequencing 670 genes mutated in haematological malignancies. SETBP1, ASXL1 and RELN mutations were significantly associated with primary chemoresistance. We identified genomic alterations not previously described in AML, together with distinct genes that were significantly overexpressed in therapy-resistant AML. Defined gene mutations were sufficient to explain primary induction failure in only a minority of cases. Thus, additional genetic or molecular mechanisms must cause primary chemoresistance in paediatric and adult AML.
منابع مشابه
The Effect of Monophosphoryl Lipid A on Maturation of DCs from Patients with Acute Myeloid Leukaemia
Background: Generation of monocyte-derived dendritic cells (MDDC) is induced in the presence of GM-CSF and IL-4, and a maturation stimulus is added to the monocyte culture to obtain mature Dendritic Cells (DCs) suitable for therapy. TNF-α is the most common cytokine used for activating DCs and generating mature MDDC either alone or in combination with other cytokines. Objective: To compare effe...
متن کاملTreatment of a Child with Refractory Acute Myeloid Leukemia with Humanized Anti-CD33 Monoclonal Antibody: A Case Report and Review of Drug Development
Background: The induction chemotherapy regimen for acute myeloid leukemia has evolved as once induction is completed patients progress through the consolidation phase and achieve remission in 76% of cases. For patients with relapsed or refractory disease, alternative chemotherapy agents are available. Monoclonal antibody therapy with biological agents, such as the immunotoxin gemtuzumab ozog...
متن کامل[Biphenotypic acute leukaemia: case reports of two paediatric patients].
INTRODUCTION Biphenotypic acute leukaemia is an uncommon type of leukaemia whose blasts co-express myeloid and B-or T-lymphoid antigens. CASE REPORT We describe two cases of paediatric patients with biphenotypic acute leukaemia. A four-year-old female patient was found to have myeloid and B-lymphoid associated antigens in the same blast cells. Cytogenetic analysis showed a Philadelphia (Ph) p...
متن کاملImproved outcome after relapse in children with acute myeloid leukaemia.
In the Nordic Society for Paediatric Haematology and Oncology paediatric study acute myeloid leukaemia (AML) 93, event-free survival was 50% and overall survival was 66%, indicating that many patients were cured following relapse. Factors influencing outcome in children with relapsed AML were investigated. The study included all 146 children in the Nordic countries diagnosed with AML between 19...
متن کاملExpression Profiling of Microarray Gene Signatures in Acute and Chronic Myeloid Leukaemia in Human Bone Marrow
Background Classification of cancer subtypes by means of microarray signatures is becoming increasingly difficult to ignore as a potential to transform pathological diagnosis nonetheless, measurement of Indicator genes in routine practice appears to be arduous. In a preceding published study, we utilized real-time PCR measurement of Indicator genes in acute lymphoid leukaemia (ALL) and acute m...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- British journal of haematology
دوره 176 1 شماره
صفحات -
تاریخ انتشار 2017