Method of diagnosis/prognosis of human chronic lymphocytic leukemia comprising the profiling of LPL/ADAM genes

• US 7,416,851 B2
• Filed: 11/08/2004
• Issued: 08/26/2008
• Est. Priority Date: 11/08/2004
• Status: Expired due to Fees

• Current Assignee: Institut Pasteur
• Original Assignee: Institut Pasteur
• Inventors: Oppezzo, Pablo, Vasconcelos Pinheiro, Yuri, Davi, Frederic, Dumas, Gerard, Settegrana, Catherine, Dighiero, Guillaume
• Primary Examiner(s): FETTEROLF, BRANDON J
• Application Number:
  US10/982,908
• Publication Number:
  US 20060099603A1
• Time in Patent Office: 1,387 Days
• Field of Search: 435/6, 435/7.1, 435/7.2, 435/7.21, 435/7.23
• US Class Current: 435/7.23
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/16 Primer sets for multiplex assays

Abstract

The present invention provides methods of diagnosis and prognosis of human chronic lymphocytic leukemia (CLL) in a subject a patient in need thereof. The methods of the present invention involve measuring the expression profile of two known genes: LPL and ADAM29; and comparing the ratio of their expression to diagnose the presence of CLL or to prognose the likelihood of developing CLL or the symptoms consistent with CLL.

Claims

1. A method for determining whether a subject diagnosed as having chronic leukemia has an aggressive form of chronic lymphocytic leukemia or an indolent form of chronic lymphocytic leukemia comprising:

obtaining a specimen from said subject,

measuring the gene expression levels of LPL and ADAM29 genes in said specimen, and

determining a LPL/ADAM29 gene expression ratio, wherein a subject is designated as having;

an indolent form of chronic lymphocytic leukemia if the LPL/ADAM29 ratio is less than one, or an aggressive form of chronic lymphocytic leukemia if the LPL/ADAM29 ratio is greater than one.

2. The method according to claim 1, wherein said specimen contains at least one biological material selected from the group consisting of peripheral mononuclear blood cells, a tissue containing B cells, and B cells.

3. The method of claim 1, in which gene expression of the LPL and ADAM29 genes is determined by RT-PCR.

4. A method for prognosing event-free survival (EFS) or overall survival (OS), or both, in a subject having chronic lymphocytic leukaemia comprising:

obtaining a specimen from a subject;

determining the gene expression levels of the LPL and ADAM29 genes in the specimen;

determining the LPL/ADAM29 gene expression ratio;

prognosing the subject as having a significant probability of event-free survival or overall survival when the LPL/ADAM29 ratio is less than one;

or

prognosing the subject as having a significant probability of a shorter event-free survival or overall survival when the LPL/ADAM29 ratio is greater than or equal to one.

5. The method of claim 4, wherein the subject is determined to have an LPL/ADAM29 ratio of less than one and is diagnosed as having an indolent form of chronic lymphocytic leukaemia characterized by greater event-free survival or greater overall survival than an aggressive form of chronic lymphocytic leukaemia.

6. The method of claim 4, wherein the subject is determined to have an LPL/ADAM29 ratio of one or more and is diagnosed as having an aggressive form of chronic lymphocytic leukaemia characterized by shorter event-free survival or shorter overall survival than an indolent form of chronic lymphocytic leukaemia.