**Abstract**

Chronic myeloid leukemia (CML) is classified as a hematological malignant rare disease by National Organization for Rare Disease (NORD, USA) based on the estimated incidence of 1–2 cases/100,000 per year internationally. CML occurs in all ages but commonly seen in the 45–55 years group. Males are slightly more affected than females. CML is one of the oldest known diseases with new faces and one of the fastest developing diseases with many extraordinary discoveries in human history of conquering the disease. CML possesses at least Nine First findings in leukemia and cancer research and even in human medical histories: the First named as leukemia in 1845, the First of a live case of CML patient diagnosed in 1846, the First used of arsenic in CML treatment in 1865, the First defined as a myeloproliferative disorder in 1951, the First finding of Philadelphia chromosome (Ph chromosome) in 1960, the First finding of chromosome 9 and 22 translocations in 1973, the First identified as a clonal hematological malignancy derived from the stage of pluripotent bone hematopoietic stem cells in 1977, the First finding of the chromosomal fusion gene-BCR-ABL as an oncogene in 1984, and the First designed target therapy of use of tyrosine kinase inhibitor (TKI) in 1998. The footprints of the studies on CML established the milestone histories. Remarkable and fascinating genetic discoveries were made of the mysteries of human diseases, the multiway translocation of Ph chromosome, and the latest issues. The association of the combination of chronic myeloid leukemia and chronic lymphocytic leukemia will be reviewed in this chapter with the aim of increasing the understanding of CML further from laboratory bench to clinical bedside.

**Keywords:** rare hematological malignancy, chronic myeloid leukemia, genetic variations, Philadelphia chromosome, BCR-ABL gene

## **1. Introduction**

Myeloproliferative neoplasm (MPN) is a rare type of hematological malignancy featured by the excessive proliferation of single or multilineages of hematopoietic cells in the bone marrow affecting fewer than six in 100,000 people. MPN mainly includes polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (MF), and chronic myeloid leukemia (CML) classified by World Health Organization (WHO) [1].

#### *Rare Diseases*

Among these types of MPN, CML, with several synonyms of chronic myelogenous leukemia, chronic granulocytic leukemia, is the most common type of myeloproliferative disorder characterized by increased proliferation of the granulocytic cell line without the loss of their capacity to differentiate.

CML consists of about 20% of all leukemias affecting individuals of all ages including children and infants with chronic, accelerated, and blast crisis phases to acute leukemia resulting in life-threatening situation [2].

CML presents as easy bleeding, splenomegaly, feeling run down or tired, fever, loss of weight without trying, loss of appetite, pain or fullness below the ribs on the left side, pale skin, and excessive sweating during sleep (night sweats) [3].

CML has a very exciting history and extraordinary findings in which it has paved the way toward clinical diagnosis and treatment. It was predicted by John Gordon in 2003 that the fascinating CML could be becoming even more fascinating from now on [4].
