Interferon-α, but not the ABL-kinase inhibitor imatinib (STI571), induces expression of myeloblastin and a specific T-cell response in chronic myeloid leukemia

Patients with chronic myeloid leukemia who maintain a complete molecular response after stopping imatinib treatment have evidence of persistent leukemia by DNA PCR

“…In the allograft setting the observation of very late relapses after a period of molecular remission provides strong evidence that CML MRD may be suppressed by an ongoing graft versus leukemia effect. 15 Cytotoxic T lymphocytes specific for leukemia-associated antigens have been demonstrated in patients treated with both interferon-a 16,17 and imatinib. 18 Further investigation is warranted to determine whether immunological reactivity against CML modifies the risk or timing of relapse when imatinib treatment is withdrawn.…”

Do we have to kill the last CML cell?

“…There is conflicting evidence as to whether similar CTL responses also occur during imatinib treatment. 45,56 In fact, rare CTLs against CML-associated antigens can be found even in the blood of normal individuals. 57 This is perhaps not surprising, given that many of the antigens associated with a CTL response in CML (and other myeloid malignancies) are widely expressed in normal cells.…”

“…[44][45][46] Complete cytogenetic responses occur in up to 20-30% of chronic-phase patients treated with IFN (±cytarabine) and such patients have a significant improvement in progression-free survival. 47 However, only a small minority of IFN-treated patients achieve a stable CMR.…”

“…IFN increases the expression of known leukaemia-associated antigens and is associated with the development of T cell responses against such antigens. 44,45 IFN may induce proliferation of CML stem cells, 42 thus contributing to stem cell exhaustion and providing a rationale for combination therapy with tyrosine kinase inhibitors, which are otherwise ineffective against quiescent CML stem cells. Extending this hypothesis, Burchert et al 52 used combination therapy with IFN and imatinib and then stopped imatinib, using IFN as maintenance treatment.…”

The German competence network ‘Acute and chronic leukemias’

“…Finally, research funded by other sources was fostered by cooperations within the network resulting in close to 200 reports published in international journals 10 within a 2-year period. Examples of successful experimental research are the recognition of myeloblastin and its characterization in CML 11 and the characterization of FLT3 mutations of prognostic relevance for AML. [12][13][14] The prolongation of survival achieved over the years for the various leukemias by the study groups forming the network are depicted in Figure 3-5.…”