Hemopathy prognosis method
This invention relates to an in vitro method for prognosis of the response to a chemotherapy of an individual suffering from chronic myeloid leukemia, comprising a. a step of measuring the expression level of at least one subgroup of genes chosen from a group of genes, b. a comparing step, and c. a step of determining a score S such that—if S is less than 1, said individual will have more than a 40% chance of responding to the chemotherapy, and—if S is greater than or equal to 1, said individual will have less than a 40% chance of responding to the chemotherapy.
1. An in vitro method of prognosis for the response to a treatment of an individual suffering from chronic myeloid leukemia, based on a leukemic biological sample taken from said individual, said method comprising:
a. measuring expression levels of at least each gene of a subgroup of genes from a group of genes,
said group of genes consisting of 25 genes, said 25 genes consisting of nucleic acid sequences SEQ ID NO: 1 to SEQ ID NO: 25,
said subgroup consisting of 7 genes, said 7 genes consisting of nucleic acid sequences SEQ ID NO: 1 to SEQ ID NO: 7,
b. comparing the expressions levels of said genes to expression levels of each of said genes obtained from a healthy biological sample, and determining a ratio for each of said genes of the expression level in the leukemic biological sample to the expression level in the healthy sample, and
c. determining a score S according to the following formula
S =Σratio i −Σratio j
where ratio i and ratio j represent respectively the ratios obtained for said genes consisting of nucleic acid sequences SEQ ID NO: i or SEQ ID NO: j,
where i and j are integers, i varying from 1 to 5 and j varying from 6 to 7, so that:
if S is less than 1, said individual will have greater than 40% chance of having a major molecular remission one year after starting treatment with a first-generation tyrosine kinase inhibitor, and
if S is greater than or equal to 1, said individual will have a less than 40% chance of having a major molecular remission one year after the start of treatment with a first-generation tyrosine kinase inhibitor.
2. The in vitro method of prognosis according to claim 1 , wherein
if S is greater than or equal to 1 and less than or equal to 2, said individual will have from a 40% to a 10% chance of having a major molecular remission one year after the start of treatment with a first-generation tyrosine kinase inhibitor.
3. The in vitro method of prognosis according to claim 1 , wherein
if S is greater than 2, said individual will have less than a 10% chance of having a major molecular remission one year after starting treatment with a first-generation tyrosine kinase inhibitor.
4. The in vitro method of prognosis according to claim 1 , wherein the value of the expression level measured is obtained by a measurement of the expression of said genes of the subgroup by PCR.
5. The in vitro method of prognosis according to claim 1 , wherein the value of the measured expression level is obtained by a measurement of the expression of said genes of the subgroup using an oligonucleotide selected from the group consisting of SEQ ID: 32 to 45.
6. The in vitro method of prognosis according to claim 1 , wherein the value of the measured expression level is obtained by a measurement of the expression of said genes, said measurement using the following oligonucleotides:
oligonucleotides SEQ ID NOS: 32 and 33 to measure the expression of the gene or consisting of the sequence of nucleic acids as set forth in SEQ ID NO: 1,
oligonucleotides SEQ ID NOS: 34 and 35 to measure the expression of the gene consisting of the sequence of nucleic acids as set forth in SEQ ID NO: 2,
oligonucleotides SEQ ID NOS: 36 and 37 to measure the expression of the gene consisting of the sequence of nucleic acids as set forth in SEQ ID NO: 3,
oligonucleotides SEQ ID NOS: 38 and 39 to measure the expression of the gene consisting of the sequence of nucleic acids as set forth in SEQ ID NO: 4,
oligonucleotides SEQ ID NOS: 40 and 41 to measure the expression of the gene consisting of the sequence of nucleic acids as set forth in SEQ ID NO: 5,
oligonucleotides SEQ ID NOS: 42 and 43 to measure the expression of the gene consisting of the sequence of nucleic acids as set forth in SEQ ID NO: 6, and
oligonucleotides SEQ ID NOS: 44 and 45 to measure the expression of the gene consisting of the sequence of nucleic acids as set forth in SEQ ID NO: 7.
7. An in vitro theranostic method of an individual suffering from chronic myeloid leukemia, comprising:
a. measuring expression level of at least one gene of a subgroup of genes chosen from a group of genes,
said group of genes consisting of 25 genes, said 25 genes consisting of nucleic acid sequences SEQ ID NO: 1 to SEQ ID NO: 25,
said subgroup consisting in 7 genes, said 7 genes consisting of the nucleic acid sequences SEQ ID NO: 1 to SEQ ID NO: 7,
a value of the expression level measured being obtained for each of said genes,
b. a step of comparing the value attributed to the preceding step with each of said genes to the value attributed to each of said genes obtained from a healthy biological sample, in order to obtain a ratio for each of said genes of the expression level in the leukemic biological sample to the expression level in the healthy sample, and
c. a step of determining a score S according to the following formula
S =Σratio i −Σratio j
where ratio i and ratio j represent respectively the ratios obtained for said genes of said subgroup consisting of nucleic acid sequences SEQ ID NO: i or SEQ ID NO: j,
where i and j are integers, i varying from 1 to 5 and j varying from 6 to 7, so that:
if S is less than 1, the chronic myeloid leukemia of said individual is chronic myeloid leukemia likely to respond preferentially to a treatment comprising a first-generation tyrosine kinase inhibitor, and
if S is greater than 2, the chronic myeloid leukemia of said individual is chronic myeloid leukemia likely to respond preferentially to a treatment comprising a second-generation tyrosine kinase inhibitor;
d. a step of administering to the individual:
a first-generation tyrosine kinase inhibitor if S is less than 1, or
a second-generation tyrosine kinase inhibitor if S is greater than 2.
8. The method according to claim 7 , wherein the first-generation tyrosine kinase inhibitor is imatinib or one of its salts.
9. The method according to claim 7 , wherein the second-generation tyrosine kinase inhibitor is selected from the group consisting of dasatinib, nilotinib, and pharmaceutically acceptable salts thereof.
10. A computer program product on an appropriate support designed to implement solely steps b and c of the method of prognosis as defined in claim 1 and comprising portions or means or instructions of program code for executing said method of prognosis when said program is executed on a computer, wherein the support is selected from the group consisting of a portable recording support, an internal memory of the computer, a device with an external memory, a proximity server, and a remote server.
11. The method according to claim 7 , wherein the first-generation tyrosine kinase inhibitor is imatinib and/or one of its salts.
12. A computer program product on an appropriate support designed to implement solely steps b and c of the theranostic method as defined in claim 7 and comprising portions or means or instructions of program code for executing said method of prognosis when said program is executed on a computer, wherein the support is selected from the group consisting of a portable recording support, an internal memory of the computer, a device with an external memory, a proximity server, and a remote server.