Selective inhibition of leukemic cell proliferation by bcr-abl antisense oligonucleotides

摘要

Leukemias characterized by the presence of the Philadelphia chromosome and the expression of the hybrid bcr-abl gene are treated with antisense oligonucleotides complementary to a target sequence of the bcr- abl mRNA transcript including the breakpoint junction. Individual chronic myelogoneous leukemia patients or Philadelphia chromosome-positive acute lymphocytic leukemia patients are treated by first sequencing the individual's bcr-abl breakpoint junction, and then administering antisense oligonucleotides complementary thereto. The oligonucleotides are designed to hybridize specifically to the bcr-abl breakpoint junction without substantial cross hybridization to untranslocated c-abl sequences. Treatment may comprise in vivo administration of antisense oligonucleotides, or ex vivo treatment such as bone marrow purging.