Balanced translocation resulting in fusion of the Abelson gene (ABL₁) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2 is the pathognomonic molecular driver of CML. The resulting BCRABL 1 fusion gene is both the diagnostic as well as therapeutic target of CML. The first agent with tyrosine kinase inhibitor activity that was licenced in 2000 for treatment of CML patients, was Imatinib, gradually followed by multiple agents with higher efficacy.

Chronic Myeloid Leukemia (CML) is a clonal disorder originated by a pluripotent hematopoietic stem cell, which presents the translocation t(9;22) (q34;q11) in 90% of the cases. This genetic abnormality is a balanced translocation between Abelson Murine Leukemia (ABL) located in chromosome 9 with the Breakpoint Cluster Region (BCR) gene at chromosome 22, generating Philadelphia chromosome (Ph) or BCR-ABL1, which codes an oncoprotein of 210 kDa. This alteration represents a hallmark in oncology and for CML research, diagnosis, and prognosis. 

Leukemia is the most common childhood malignancy and cause of pediatric cancer death. Significant advances in the cure rates of B-cell acute lymphoblastic leukemia (B-ALL) and T-cell acute lymphoblastic leukemia (T-ALL) have been achieved; however, patients with refractory or relapsed B-ALL or T-ALL continue to have poor outcomes. Immunotherapy is a revolutionary treatment aimed to improve survival and reduce the toxicity of chemotherapy by harnessing the patient’s own immune system to target cancer cells.

Significant milestones and seminal discoveries during 1674-1966, by individuals who have made crucial contributions toward progress in the diagnosis of hematologic neoplasms as we understand today are depicted chronologically. It is notable that the path to progress in the understanding of disease and neoplasms initially took centuries for significant discoveries (17^th-18^th centuries), and subsequently, many decades (19^th-20^th centuries) for a breakthrough or a change from the prevailing norm. 

Chronic lymphoid leukemia (CLL) is a malignant hematological disease characterized by the accumulation of mature lymphocytes with a defect in the induction of apoptosis that massively accumulate in peripheral blood (PB), bone marrow (BM) and lymphoid tissues.