Chronic Myeloid Leukemia: From Targeted Therapy to Treatment-Free Remission

Chronic Myeloid Leukemia (CML) is a hematopoietic stem cell disorder driven by the BCR-ABL1 oncogene which encodes for a non-receptor tyrosine kinase with constitutive deregulated kinase activity causing clonal expansion of leukemic stem cells. To date, the first line treatment for CML patients concerns the use of anti-ABL1 kinase drugs, known as Tyrosine Kinase Inhibitors (TKIs). A crucial aspect regarding CML and disease progression concerns the TKIs insensitivity properties of LSCs. In fact, although TKIs arrest the proliferation of committed Ph+ cells, they are ineffective to induce apoptosis of LSCs that preserving their self-renewal properties representing a reservoir of the disease. This event causes disease relapse promoting the proliferation of a more aggressive and TKIs resistant leukemic clone.

The therapeutic landscape for CML now includes several approved ABL-directed inhibitors, known as Tyrosine Kinase Inhibitors, and most patients with optimal response have a normal life expectancy. Although studies on CML generated crucial progresses to understand cell biology, patients management and molecular disease monitoring, several critical issues are still under investigation, including: detection of minimal residual disease employing techniques such next generation sequencing (NGS), digital PCR (dPCR) or more innovative methods, eradication of leukemic stem cells (LSCs), new therapeutic approaches and the possibility to attempt TKIs discontinuation achieving treatment-free remission (TFR).

In this Research Topic several aspects concerning new perspectives on CML prognosis will be covered. The Topic will also invite submissions on:

- CML therapy
- LSCs
- resistance mechanisms
- molecular monitoring
- TKIs discontinuation