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Chromosomal abnormalities in Ph- cells of patients on imatinib

2003; Elsevier BV; Volume: 102; Issue: 7 Linguagem: Inglês

10.1182/blood-2003-06-1943

1528-0020

Mary Frances McMullin, Mervyn Humphreys, Jenny Byrne, Nigel H. Russell, R Cuthbert, Michael O’Dwyer,

Myeloproliferative Neoplasms: Diagnosis and Treatment

achieved after 3 weeks of therapy.At 8 weeks after initiation of imatinib therapy, semiquantitative RT-PCR analysis showed a 99% reduction in H4/PDGF␤R expression in peripheral blood compared with blood samples taken prior to treatment (Figure 1D).The patient remains in complete response after one year of therapy.Imatinib mesylate has been shown to efficiently inhibit the activity of certain tyrosine kinases, including BCR-ABL, c-Kit, PDGF␤R, PDGF␣R, and ARG kinase. [5]6] Thus to further investigate the role of chimeric protein H4/PDGF␤R, imatinib mesylate was tested in bone marrow primary cultures.Interestingly, bone marrow primary cultures from the t(5;10) patient displayed marked apoptosis when treated with imatinib (Figure 1C).Our results demonstrate the efficiency of imatinib in the treatment of patients displaying the translocation involving H4 and PDGF␤R genes.Imatinib binds tightly into the adenosine triphosphate (ATP)-binding pocket within the tyrosine kinase domain of BCR-ABL, 7 and we predict a similar mode of action with PDGF␤R.Hence, the observed positive response strongly suggests that inhibition of PDGF␤R activity may also be effective in other myeloproliferative diseases involving this tyrosine kinase receptor.