Methods of diagnosing and treating B cell acute lymphoblastic leukemia

Patent metadata

Field	Value
Publication number	US-10106834-B2
Application number	US-201415028515-A
Country	US
Kind code	B2
Filing date	Oct 9, 2014
Priority date	Oct 9, 2013
Publication date	Oct 23, 2018
Grant date	Oct 23, 2018

Abstract

Methods for the diagnosis and treatment of B cell Acute Lymphoblastic Leukemia (B-ALL), based in part on the detection and/or inhibition of Focal Adhesion Kinase (FAK), e.g., phosphorylated FAK (pFAK).

First claim

What is claimed is:

1. A method of treating a subject who has B cell acute lymphoblastic leukemia (B-ALL), comprising:
(i) identifying a subject comprising leukemic cells having a mutation in IKZF1, wherein the mutation results in haploinsufficiency or expression of a dominant negative form of Ikaros and/or in hyperactivation of FAK activity; and
(ii) administering a therapeutically effective amount of VS-4718 and dasatinib to the subject.

2. The method of claim 1 , further comprising selecting the subject for treatment comprising:
obtaining a sample from the subject comprising B cells that are known or suspected to be leukemic; and
(i) performing an assay to determine a level of FAK activity in the sample;
comparing the level of FAK activity in the sample to a reference level of FAK activity;
identifying a subject as having cells with a level of FAK activity that is above the reference level; or
(ii) performing an assay to detect the presence or absence of a mutation in IKZF1 in the cells;
identifying a subject as having cells with a mutation in IKZF1; and
selecting the identified subject for treatment with an inhibitor of FAK.

3. The method of claim 2 , wherein performing an assay to determine a level of FAK activity in the sample comprises determining a level of phosphorylated FAK in the subject.

4. The method of claim 2 , wherein the mutation in IKZF1 results in haploinsufficiency or expression of a dominant-negative isoform of Ikaros.

5. The method of claim 2 , wherein the mutation in IKZF1 results in hyperactivation of FAK activity.

6. The method of claim 2 , wherein the subject has been diagnosed with B-ALL.

7. The method of claim 2 , wherein the subject has not been diagnosed with B-ALL.

8. The method of claim 2 , wherein the sample comprises peripheral blood B cells.

9. The method of claim 2 , wherein the sample comprises bone marrow B cells.

Assignees

• Massachusetts Gen Hospital
• Tufts Medical Ct Inc

Inventors

• Georgopoulos Katia
• Etten Richard A
• Joshi Ila

Classifications

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title

• A61K31/7088

  Compounds having three or more nucleosides or nucleotides · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title

• G01N33/5011

  for testing antineoplastic activity · CPC title