CD38 as a prognostic indicator in B cell chronic lymphocytic leukemia
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.
1. A method of treating B-cell chronic lymphocytic leukemia (B-CLL) in a subject comprising:
a) receiving an identification of the subject as having an unmutated Ig V H sequence in a B-CLL cell; and
b) administering one or more of a chemotherapy, radiation therapy, surgery, immunotherapy or transplantation B-CLL therapy to the subject identified as having an unmutated Ig V H sequence in a B-CLL cell,
wherein the identification of the subject as having an unmutated IgV H sequence in a B-CLL cell is obtained by determining whether a blood sample or bone marrow sample from the subject comprises B-CLL cells that have Ig V H gene mutations, wherein the presence of Ig V H gene mutations is determined by establishing whether the DNA sequence of an Ig V H gene of B-CLL cells of the sample is >2% different from a corresponding non-mutated germline DNA sequence of the Ig V H gene, wherein the absence of such Ig V H genes that are >2% different from the germline gene in the sample identifies the subject as having an unmutated Ig V H sequence.
2. The method of claim 1 , wherein the B-CLL therapy administered to the subject is a chemotherapy.
3. The method of claim 1 , wherein the B-CLL therapy administered to the subject comprises fludarabine.
4. The method of claim 1 , wherein the B-CLL therapy administered to the subject comprises a continuous chemotherapy.
5. The method of claim 1 , wherein the B-CLL therapy administered to the subject comprises a chemotherapy utilizing two or more agents or regimens.
6. The method of claim 1 , wherein the B-CLL therapy administered to the subject comprises a radiation therapy, surgery, immunotherapy or transplantation.
7. A method of treating a subject for B-cell chronic lymphocytic leukemia (B-CLL) comprising:
receiving identification of a B-CLL subject as having a V gene mutation status indicating an aggressive B-CLL disease course; and
administering one or more of a chemotherapy, radiation therapy, surgery, immunotherapy or transplantation B-CLL treatment to the subject identified as having a V gene mutation status indicating an aggressive B-CLL disease course,
wherein the B-CLL subject is identified as having V gene mutation status indicating an aggressive B-CLL disease course by a method comprising determining whether a blood sample or bone marrow sample from the subject comprises B-CLL cells that have Ig V gene mutations by determining whether a DNA sequence of either the Ig V H gene or Ig V L gene of the B-CLL cells of the sample is >2% different from a corresponding non-mutated germline DNA sequence of the Ig V H gene or Ig V L gene, wherein the absence of Ig V H gene or Ig V L gene in the B-CLL cells that is >2% different from the corresponding non-mutated germline gene identifies the subject as having an aggressive disease course.
8. The method of claim 7 , wherein the subject is identified by a method comprising isolating nucleic acid from the B-CLL cells of the sample, amplifying a nucleic acid thereof by contacting the nucleic acid with a sense V H leader family-specific primer, and sequencing a nucleic acid thereof corresponding to an Ig V H gene of the B-CLL cells.
9. The method of claim 7 , wherein the nucleic acid isolated from the cells of the sample is RNA, and wherein the RNA is reverse transcribed into cDNA by contacting the RNA with a reverse transcriptase prior to sequencing.
10. The method of claim 7 , wherein the subject is identified by a method further comprising obtaining the B-CLL cells from the blood sample prior to isolating nucleic acid from the B-CLL cells.
11. The method of claim 7 , wherein the subject is identified by a method comprising sequencing the nucleic acid with an automated sequencer.
12. The method of claim 7 , wherein the B-CLL therapy administered to the subject is a chemotherapy.
13. The method of claim 7 , wherein the B-CLL therapy administered to the subject comprises fludarabine.
14. The method of claim 7 , wherein the B-CLL therapy administered to the subject comprises a continuous chemotherapy.
15. The method of claim 7 , wherein the B-CLL therapy administered to the subject comprises a chemotherapy utilizing two or more agents or regimens.
16. The method of claim 7 , wherein the B-CLL therapy administered to the subject comprises a radiation therapy, surgery, immunotherapy or transplantation.