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Milestones in Chronic Myeloid Leukemia

An article on targeted therapy for chronic myeloid leukemia by Brian Druker, MD, and these accompanying milestones were published in December 2008 as part of the special ASH anniversary brochure, 50 Years in Hematology: Research That Revolutionized Patient Care.

1845 John Hughes Bennett and Rudolph Virchow describe the first cases of CML.
1960 Peter Nowell and David Hungerford identify an abnormal chromosome in the blood cells and bone marrow of patients with CML.
1973 Janet Rowley determines that the abnormal chromosome identified by Nowell and Hungerford results from the exchange of genetic material between two chromosomes.
John Groffen, Nora Heisterkamp, Gerard Grosveld, E. Cannani, David Baltimore, and Owen Witte show that an abnormal gene and protein called BCR-ABL is produced as a consequence of the chromosome rearrangement that characterizes CML.
1987 Nicholas Lydon and Alex Matter begin a drug discovery program to target proteins such as BCR-ABL in collaboration with Brian Druker, Thomas Roberts, and Charles Stiles.
1993 Brian Druker's laboratory shows that STI571 (imatinib) is the best of the compounds developed by Nicholas Lydon's group at specifically targeting and killing CML cells.
1998 Brian Druker, Charles Sawyers, and Moshe Talpaz begin clinical trials of imatinib.
Imatinib is FDA-approved for patients with CML.
Charles Sawyers, Brian Druker, Andreas Hochhaus, and François-Xavier Mahon report that mutations of BCR-ABL are the major mechanism of resistance to imatinib.
2006 Follow-up data show a 95 percent five-year survival for patients with CML treated with imatinib.
Dasatinib and nilotinib are FDA-approved for patients with imatinib resistance.