IDENTIFICATION OF A JAK2 MUTATION IN POLYCYTHEMIA VERA

• US 20090162849A1
• Filed: 09/19/2008
• Published: 06/25/2009
• Est. Priority Date: 10/27/2004
• Status: Active Grant

• Current Assignee: Ipsogen SA
• Original Assignee: Ipsogen SA
• Inventors: Le Couedic, Jean-Pierre, Casadevall, Nicole, Ugo, Valerie, James, Chloe, VAINCHENKER, William
• Granted Patent: US 8,637,235 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 9/1205 Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases
• CPC Class Codes: C12Q 1/6813 Hybridisation assays
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: G01N 2333/91215 with a definite EC number (2.7.1.-)
• CPC Class Codes: G01N 2500/04 Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
• CPC Class Codes: G01N 33/57426 leukemia
• CPC Class Codes: G01N 33/57496 involving intracellular compounds

Abstract

The present invention concerns the V617F variant of the protein-tyrosine kinase JAK2, said variant being responsible for Vaquez Polyglobulia. The invention also relates to a first intention diagnostic method for erythrocytosis and thrombocytosis allowing their association with myeloproliferative disorders, or to the detection of the JAK2 V617F variant in myeloproliferative disorders allowing their reclassification in a new nosological group.

Claims

1-20. -20. (canceled)

21. An in vitro method to determine the presence or absence of the V617F variant in the JAK2 gene in a human patient comprising:

a) obtaining and analyzing a nucleic acid sample from the human patient;

b) detecting the presence or absence of the V617F variant in the JAK2 gene; and

c) recording the presence or absence of the V617F variant in the JAK2 gene.

22. The method of claim 21, wherein the method determines if a human patient is currently suffering from or is likely to develop a myeloproliferative disorder selected from the group consisting of Polycythemia Vera, essential thrombocythemia, and idiopathic myelofibrosis.

23. The method of claim 21, wherein the analyzing comprises:

a) sequencing a region of the nucleic acid sample comprising position 2343 of SEQ ID NO 2;

or

b) hybridizing under stringent conditions the nucleic acid sample with at least one probe comprising at least 10 consecutive nucleotides of SEQ ID NO 2 comprising position 2343 of SEQ ID NO 2.

24. The method of claim 21, wherein analyzing comprises amplifying a region of the nucleic acid sample comprising position 2343 of SEQ ID NO 2 with at least one primer and hybridizing under stringent conditions the nucleic acid sample with at least one probe comprising at least 10 consecutive nucleotides of SEQ ID NO 2 comprising position 2343 of SEQ ID NO 2.

25. The method of claim 23, wherein the at least one probe is labeled with at least one marker and detecting comprises detection of the signal produced by the at least one probe.

26. The method of claim 25, wherein the hybridizing comprises hybridizing with at least two probes.

27. The method of claim 24, wherein the nucleic acid sample is mRNA and wherein amplifying comprises amplifying by reverse transcriptase-polymerase chain reaction.

28. The method of claim 21, wherein the V617F variant in the JAK2 gene is a T in the JAK2 gene at position 2343 of SEQ ID NO 2 in the sample.