Method for the treatment of acute myeloid leukemia

A therapeutic composition, active ingredient technology, applied in the field of molecular medicine, capable of addressing issues such as new treatments for AML without insights, specific genes or microRNAs that have not yet been identified

CN102421899AInactive Publication Date: 2012-04-18ERASMUS UNIV MEDICAL CENT ROTTERDAM ERASMUS MC
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Publication Date
2012-04-18
Estimated Expiration
Not applicable · inactive patent

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Abstract

The invention is in the field of molecular medicine and provides methods for the treatment of acute myeloid leukemia. These methods are based on the observation that microRNA-9 and microRNA-9* are involved in the pathogenesis of the disease in that the overexpression of microRNA-9 / 9* block myeloid differentiation in vitro. More in particular, microRNA-9 / 9* were found to play a role in leukemic transformation in acute myeloid leukemia.
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Description

field of invention

[0001] The invention belongs to the field of molecular medicine and provides a method for treating acute myelogenous leukemia. These approaches are based on the observation that microRNA-9 and / or microRNA-9* (microRNA-9 / 9*) are involved in the pathogenesis of the disease, since overexpression of microRNA-9 / 9* blocks myeloid differentiation in vitro. More specifically, microRNA-9 / 9* was found to play a role in leukemic transformation in acute myeloid leukemia. Background of the invention

[0002] Acute myelogenous leukemia (AML) is a remarkably heterogeneous malignancy disease characterized by uncontrolled clonal proliferation of hematopoietic progenitor cells blocked at different developmental stages. The altered clinical biology and prognosis are mainly driven by somatic genetic aberrations such as t(15;17), t(8;21), inv(16), 11q23, 3q26 aberrations and monochromosomal karyotypes (1-3) as well as various determined by a genetic mutation. Prominent exam...

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Embodiment Construction

[0030] We found that microRNA-9 / 9* plays a role in leukemic transformation in acute myeloid leukemia AML.

[0031] When used herein, the term miRNA 9 / 9* is intended to refer to microRNA 9 and / or microRNA 9*.

[0032]MicroRNAs are single-stranded RNAs of 18-25 nucleotides and are produced from precursor molecules. microRNAs are encoded in the genome and transcribed by RNA polymerase II into primary transcripts called pri-microRNAs, which are processed in the nucleus into one or more pre-microRNAs by nuclear RNase III Drosha and the double-stranded RNA-binding protein Pasha / DGCR8 microRNA (pre-microRNA) (32, 33). In the cytoplasm, another RNaseIII called Dicer further processes the pre-microRNA into a double-stranded, 23-nucleotide mature microRNA. This microRNA duplex (34) comprises a strand incorporated into the RNA-induced silencing complex (RISC) (microRNA strand) and a complementary strand (microRNA* strand), which is normally degraded.

[0033] There are several excepti...