**4. Chronic myelomonocytic leukemia (CMML)**

unidentified. However, we know that consecutive genomic mutations and epigenetic modifications lead to the progression of the disease. Alterations in important genes have been characterized leading to the development of novel targeted therapeutic strategies. However, significant variations in the genetic and the epigenetic of AML are found among patients. Thus, development of efficient treatment of AML remains a significant clinical

Current AML treatment is generally based on classical chemotherapy, targeted therapy, and stem cell transplantation. The emergence of personalized medicine is still underway. Optimal biological information leading to patient selection and individual therapy are

In addition to the age of AML patients, cytogenetics of the tumor and clinical appreciations are fundamental for the prognosis and the success of the treatment. Promyelocytic leukemia is the subset of AML with the highest proportion of cure rate. Patients are benefiting from targeted therapy such as all-transretinoic acid treatment. Currently, several other targeted

The limiting parameters for AML targeted therapy are the tumor heterogeneity and its variability during the course of disease and therapy, resulting in unpredictable response, and constitute the current challenge for establishing successful personalized therapeutic

CML is a myeloproliferative disorder characterized by the presence of the BCR-ABL oncogene fusion protein, resulting from reciprocal translocation between chromosomes 9 and 22 [t(9;22)], commonly designed by Philadelphia chromosome (Ph chromosome) (Ref). As a result, Bcr-Abl tyrosine kinase becomes constitutively activated and triggers apoptosis resistance and other biological alterations responsible for CML pathogenesis. With the introduction of tyrosine kinase inhibitors (TKIs), significant benefits for CML patients are currently achieved. Nilotinib, dasatinib, and imatinib are the commonly TKIs small molecules used in the clinic for the treatment of CML. These inhibitors are designed to block the adenosine triphosphate-binding site of the Bcr-Abl tyrosine kinase and inhibit the activation of down-

The success of TKI therapy is associated with the reduction of BCR-ABL1 transcript levels in the CML patients. Current guidelines refer to major molecular response (MMR) for the BCR-ABL1 level not exceeding 0.1% or deep molecular response (DMR) for the BCR-ABL1 level not exceeding 0.01%. DMR can be achieved in almost 50% of CML patients who stopped TKI treatments. However, important questions remain regarding the mechanisms leading to CML remission and lack of relapse. Addressing such questions will help identify biomarkers that could predict which patient could discontinue TKI therapy without relapse and also deter-

challenge.

4 Myeloid Leukemia

uncommon.

regimens.

therapies are available.

**3. Chronic myeloid leukemia (CML)**

mine the long-term success of the treatment.

stream effector proteins, responsible for CML exacerbations.

CMML displays irregular features, varying from myelodysplastic to myeloproliferative. The majority of CMML patients show persistent somatic mutations. Around 15% of CMML can evolve to AML, and when this transition occurs, a poor prognosis is predicted. Many chemotherapy regimens for CMML have been used with only limited success. Bone marrow transplantation or stem cell transplantation appears to be more effective.
