CD38 as a prognostic indicator in B cell chronic lymphocytic leukemia

• US 7,316,906 B2
• Filed: 08/02/2002
• Issued: 01/08/2008
• Est. Priority Date: 10/08/1999
• Status: Expired due to Term

• Current Assignee: The Feinstein Institutes For Medical Research
• Original Assignee: The Feinstein Institute for Medical Research (Northwell Health, Inc.)
• Inventors: Wasil, Tarun, Chiorazzi, Nicholas, Damle, Rajendra N.
• Primary Examiner(s): UNGAR, SUSAN NMN
• Application Number:
  US10/211,394
• Publication Number:
  US 20030082593A1
• Time in Patent Office: 1,985 Days
• Field of Search: 435/7.1
• US Class Current: 435/7.1
• CPC Class Codes: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 15/1456 without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals
• CPC Class Codes: G01N 15/149 specially adapted for sorting particles, e.g. by their size or optical properties
• CPC Class Codes: G01N 33/57426 leukemia

Abstract

The subject invention discloses a method for determining the prognosis and probable clinical course of a subject diagnosed with B-CLL. Specifically, the invention involves comparing CD38 expression in a biological sample from the subject containing B-CLL cells to a baseline level of CD38 expression, wherein an elevated level of CD38 expression in relation to the baseline level of CD38 expression may indicate poor prognosis or aggressive course of disease in the subject. Also disclosed is a method for determining whether the Ig V genes of the B-CLL cells of a B-CLL patient are mutated, comprising comparing CD38 expression in a biological sample from the subject containing B-CLL cells to a baseline level of CD38 expression, wherein a lower level of CD38 expression in relation to the baseline level indicates IG V gene mutation.

Claims

1. A method for determining indications of the prognosis of and aggressiveness of disease in a subject with B cell chronic lymphocytic leukemia (“

B-CLL”

), the method comprising;

measuring CD38 expression by B-CLL cells in a blood sample from the subject;

determining the percentage of B-CLL cells in the sample that are CD38⁺; and

comparing said percentage to a cut-off value,

wherein a percentage of CD38⁺ B-CLL cells from the subject that is greater than or equal to the cut-off value indicates a poor prognosis and an aggressive disease course and a percentage of CD38⁺ B-CLL cells from the subject that is less than the cut-off value indicates an indolent disease course,

wherein the cut-off value is determined by;

measuring CD38 expression by B-CLL cells in a blood sample from each of a cohort of B-CLL patients;

determining the percentage of B-CLL cells that are CD38⁺ in each of the cohort patients;

determining whether the B-CLL in each of the cohort patients is aggressive or indolent; and

plotting the percentage of B-CLL cells that are CD38⁺ in the cohort patients vs. aggressiveness or indolence in the cohort patients to establish a cut-off value that distinguishes between patients with aggressive disease and patients with indolent disease.

2. The method of claim 1, wherein B-CLL cells are determined as CD5⁺ and CD19⁺.

3. The method of claim 1, wherein CD38 expression of B-CLL cells is determined using flow cytometry.

4. The method of claim 1, wherein the B-CLL patients are IgM⁺ B-CLL patients.

5. The method of claim 1, wherein measuring CD38 expression by B-CLL cells in a blood sample from each cohort patient is determined prior to measuring CD38expression by B-CLL cells in a blood sample from the subject.

6. A method for evaluating whether a subject with B cell chronic lymphocytic leukemia (“

B-CLL”

) should undergo an aggressive course of treatment, the method comprising

measuring CD38 expression by B-CLL cells in a blood sample from the subject;

determining the percentage of B-CLL cells in the sample that are CD38⁺; and

comparing said percentage to a cut-off value,

wherein a percentage of CD38⁺ B-CLL cells from the subject that is greater than or equal to the cut-off value indicates the subject should undergo an aggressive course of treatment and a percentage of CD38⁺ B-CLL cells from the subject that is less than the cut-off value indicates the subject should not undergo an aggressive course of treatment,

wherein the cut-off value is determined by;

measuring CD38 expression by B-CLL cells in a blood sample from each of a cohort of B-CLL patients;

determining the percentage of B-CLL cells that are CD38⁺ in each of the cohort patients;

determining whether the B-CLL in each of the cohort patients is aggressive or indolent; and

plotting the percentage of B-CLL cells that are CD38⁺ in the cohort patients vs. aggressiveness or indolence in the cohort patients to establish a cut-off value that distinguishes between patients with aggressive disease and patients with indolent disease.

7. The method of claim 6, wherein B-CLL cells are determined as CD5⁺ and CD19⁺.

8. The method of claim 6, wherein CD38 expression of B-CLL cells is determined using flow cytometry.

9. The method of claim 6, wherein the B-CLL patients are IgM⁺ B-CLL patients.

10. The method of claim 6, wherein measuring CD38 expression by B-CLL cells in a blood sample from each cohort patient is determined prior to measuring CD38 expression by B-CLL cells in a blood sample from the subject.