Methods for assessing patients with acute myeloid leukemia

An acute myeloid and leukemia technology, applied in the field of predicting the prognosis of patients with acute myeloid leukemia, can solve the problems of unseen response rate and differences

Inactive Publication Date: 2005-12-07
VERIDEX LCC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In fact, although early clinical studies were designed around populations with a high frequency of ras mutations, such as a

Method used

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  • Methods for assessing patients with acute myeloid leukemia
  • Methods for assessing patients with acute myeloid leukemia
  • Methods for assessing patients with acute myeloid leukemia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0105] Clinical evaluation and response definition

[0106] The current study is part of an open label, multi-center, non-comparative phase 2 clinical study in which tipifarnib was used at an initial oral dose of 600 mg twice a day (bid) Patients with relapsed or refractory AML (Harousseau et al. (2003)) are treated for 21 consecutive days at the beginning of each 28-day cycle. The patients were divided into 2 groups, namely those with relapsed AML and those with intractable AML. A total of 252 patients (135 relapsed and 117 refractory) were treated. Eight patients chose to provide bone marrow samples for RNA microarray analysis, for which individual consent was required. The overall response rate is relatively low in this study. Therefore, for the purpose of gene expression profiling, the response to tipifarnib is defined as an objective response (complete remission [CR], complete remission with incomplete platelet recovery [CRp] or partial remission [PR]). Patients with stable...

Embodiment 2

[0131] Identify genes that are differentially expressed between responders and non-responders

[0132] We next performed a supervised analysis using gene expression data to identify genes that are differentially expressed between all responders and at least 40% of non-responders. These criteria were selected to identify genes that can predict the response to tipifarnib with the highest level of sensitivity possible. From 11,723 genes, a total of 19 genes (Table 4) that were able to distinguish between responders and non-responders (Table 5) and gave a significant P value (P<0.05) in the t-test were identified. These genes include those involved in signal transduction, apoptosis, cell proliferation, tumorigenesis and, potentially, FTI biology (ARHH, AKAP13, IL3RA).

[0133] Seq ID NO

Gene symbol

Gene ID

Function description

5

1

6

7

8

9

10

11

12

13

14

15

AHR

AKAP13

MINA53

IDS

OPN3

GPR10...

Embodiment 3

[0152] Analysis of prognostic gene markers in AML

[0153] 3 Gene markers can predict prognosis that has nothing to do with the type of drug treatment. To measure this, we first evaluated gene expression markers recently identified in newly diagnosed AML patients who were treated with traditional chemotherapy. Bullinger et al. (2004). The cDNA array was used to define this marker, and we therefore first matched these genes with the probes present on the Affymetrix gene chip. The 167 probe sets of 133 predictive genes identified by Bullinger et al. (corresponding to 103 unique genes) were matched with the Affymetrix U133A chip. The 3 genes identified in our current analysis are not in the 133 gene list of Bullinger et al. SEQ ID NOs: 23-189. Two main patient groups were defined by using these 167 probe groups for hierarchical clustering (Figure 8A). Kaplan-Meier analysis showed that these clusters were clearly divided into patients with good and poor prognosis (Figure 8B, p=0.000...

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Abstract

Methods for treating cancer, and preferably hematological malignancy, patients include analyzing gene expression profiles and/or molecular markers of a patient to determine status and/or prognosis of the patient. The invention also provides methods of analyzing whether a non-relapsed or non-refractory patient is likely to respond to treatment with farnesyl transferase inhibitors (FTIs) and, optionally, other therapeutics. The methods are also useful for monitoring patient therapy and for selecting a course of therapy. Genes modulated in response to FTI treatment are provided and are used in formulating the profiles.

Description

[0001] Cross reference with related applications [0002] no [0003] Statement regarding federally funded research or development [0004] no [0005] Reference to "Sequence Listing" [0006] This article hereby incorporates the "Sequence List" listed in the appendix as a reference. Background of the invention [0007] In this application, US Patent Application Serial No. 60 / 637,265 filed on December 17, 2004 is incorporated by reference. [0008] The invention relates to the diagnosis, prognosis and treatment of acute myeloid leukemia (AML) on the basis of molecular marker detection and / or gene expression analysis. [0009] The current karyotype analysis is effective in providing prognostic value, and it is also used to identify different biological subtypes of AML. In addition, mutations in genes such as FLT3, c-KIT, AML1, GATA1, CEBPA and N-RAS are involved in the pathogenesis of the disease. Obviously screening for FLT3 and CEBPA mutations can be divided into groups with diffe...

Claims

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Application Information

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IPC IPC(8): G01N33/53A61K39/39A61K45/00A61K48/00A61P35/00A61P35/02A61P43/00C12M1/00C12N15/09C12Q1/00C12Q1/68G01N37/00
CPCC12Q2600/112C12Q2600/154C12Q1/6886C12Q2600/158C12Q2600/106C12Q2600/118A61P35/00A61P35/02A61P43/00G01N33/49G01N33/57426
Inventor M·拉波尼
Owner VERIDEX LCC
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