Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) is a neoplastic disease characterized by a reciprocal balanced translocation between chromosomes 9 and 22, namely the Philadelphia chromosome, which encodes the BCR-ABL1 fusion protein, a constitutively active tyrosine kinase. Five tyrosine kinase inhibitors (TKIs) targeting the ATP-catalytic site of the BCR-ABL1 protein are approved: the introduction of these drugs into clinical practice drastically changed the outcome of CML patients, with a lifespan actually similar to that of general population. Imatinib, the first generation TKI, has improved the overall survival to more than 90%: some patients develop resistance and half of clinical resistance is due to the onset of mutations of ATP-binding site, but also intolerance in the long-term can be associated to treatment failure. Second and third generation TKIs entered into clinical practice, able to rescue about 40-50% of resistant patients, but with increasing probabilities of off-target effects in the long term. Recent studies showed that about 40-50% patients that achieved stable and deep molecular responses with every drug available can remain disease free after treatment discontinuation, but with the evidence of persistence of Ph+ leukemic stem cells and residual disease.

The special issue on chronic myeloid leukemia will cover the following topics:

1. The biology of CML disease: characteristics of Ph+ leukemic stem cells
2. Monitoring CML in 2018: cytogenetic, molecular (RQ-PCR and ddPCR) and mutation analysis
3. Tyrosine kinase inhibitors available for CML treatment: safety and efficacy
4. Treatment-free remission in CML: new endpoint for all patients?
5. New approaches and combination for CML treatment
6. The management of CML in advanced phase