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Methods of treating acute myeloid leukemia with an FLT3 mutation

一种骨髓性白血病、酪氨酸激酶的技术，应用在有机活性成分、含有效成分的医用配制品、医药配方等方向，能够解决没有被批准急性骨髓性白血病等问题

Inactive Publication Date: 2016-10-12
BIOKINE THERAPEUTICS LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Several classes of FMS tyrosine kinase 3 inhibitors are currently under clinical investigation, but none have been approved to date for the treatment of acute myeloid leukemia with FMS-like tyrosine kinase 3 mutations (Fathi and Chen, Am. J. Blood Res. Blood Res.1:175-189,2011)

Method used

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  • Methods of treating acute myeloid leukemia with an FLT3 mutation
  • Methods of treating acute myeloid leukemia with an FLT3 mutation
  • Methods of treating acute myeloid leukemia with an FLT3 mutation

Examples

Experimental program
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Effect test

example 1

[0137] Effect of the CXCR4 antagonistic peptide BL-8040, alone or in combination with chemotherapeutic agents, on the in vitro survival of acute myeloid leukemia cells

[0138] Materials and methods:

[0139] Potion:

[0140] BL-8040 (4F-benzoyl-TN14003 (4F-benzoyl-TN14003); SEQ ID NO: 1) was synthesized by MSD N.V. and lyophilized.

[0141] ARA-C (cytarabine) was purchased from Israel Hadassah cytotoxica pharmaceutical factory.

[0142] AC220 (quizartinib) was purchased from Selleck chemicals pharmaceutical factory in the United States.

[0143] Acute myeloid leukemia cells:

[0144] The following cell lines were obtained from ATCC: MV4-11 (human acute myeloid leukemia cells with FMS-like tyrosine kinase 3 internal tandem repeat mutation) and HL60 (human acute myeloid leukemia cells with wild-type FMS-like tyrosine kinase 3 cells; FMS-like tyrosine kinase 3-WT).

[0145] Acute myeloid leukemia cells with FMS-like tyrosine kinase 3 internal tandem repeat mutations were ob...

example 2

[0165] In an acute myeloid leukemia model with a FMS-like tyrosine kinase 3 internal tandem duplication, BL-8040 caused apoptosis of acute myeloid leukemia cells, which was further increased in the presence of AC220.

[0166] The present inventors studied the effects of BL-8040 alone on the survival and cell death of acute myeloid leukemia cells with FMS-like tyrosine mutations and in combination with the FMS-like tyrosine kinase 3 inhibitor AC220.

[0167] Methods: Human acute myeloid leukemia MV4-11 cells (FMS-like tyrosine kinase 3 internal tandem repeat) were used. Cells were cultured in vitro for 48 hours in the presence of BL-8040 (20 μM), AC220 (50 nM), or a combination thereof. Levels of viable cells, percent cell death were assessed by FACS.

[0168] In the in vivo study, an acute myeloid leukemia model in NOD SCID gamma (NSG) mice implanted with MV4-11 cells was used. Mice were treated daily for three weeks after implantation with subcutaneous injections of BL-8040...

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Abstract

There is provided a method of treating acute myeloid leukemia (AML). The method includes the step of administering to a patient having AML with a FMS-like tyrosine kinase 3 (FLT3)-mutation a therapeutically effective amount of a CXCR4- antagonistic peptide.

Description

technical field [0001] The present invention relates to a method for treating acute myeloid leukemia (AML), and more particularly relates to the use of CXCR4 antagonist peptide in treating acute myeloid leukemia with FMS-like tyrosine kinase 3 mutation. Background technique [0002] Acute myeloid leukemia is a heterogeneous group of diseases characterized by the uncontrolled proliferation and reduced ability of hematopoietic stem cells (hematopoietic stem cells) and progenitor cells (blasts) to differentiate into mature cells (Estey et al. by Lancet 368:1894-1907, 2006). Although the use of traditional chemotherapy, many patients with acute myeloid leukemia can be completely remission (complete remission, CR), but most patients with acute myeloid leukemia still relapse eventually. Patients with FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations have a particularly high relapse rate. Internal tandem repeat mutations of FMS-like tyrosine kinase 3 a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/10A61K31/5377A61K31/7068
CPCA61K9/0019A61K31/5377A61K31/7068A61K38/10A61K2300/00A61P35/00A61P35/02A61P43/00A61K45/06
Inventor 阿姆农·佩莱德米哈尔·亚伯拉罕
Owner BIOKINE THERAPEUTICS LTD
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