Chronic Myeloid Leukemia Disease Background

Introduction

Chronic myeloid leukemia (CML), also known as chronic myelogenous, myelocytic, or chronic granulocytic leukemia, is a myeloid disorder associated with the Philadelphia (Ph) chromosome, t(9;22)(q34;q11), resulting in the fusion of the breakpoint cluster region (BCR) and Abelson murine leukemia (ABL1) genes. CML has 3 phases, chronic, accelerated, and blastic.

Epidemiology

Chronic myeloid leukemia accounts for roughly 15% of all leukemias in adults. The median age of CML in Western countries at presentation is >50 years old. Its annual incidence is 1 to2 per 100,000 with a slight male predominance. So far in 2025, there have been 9,560 documented new cases, representing 0.5% of all new cancer cases. Prior to the advent of tyrosine kinase inhibitor (TKI), CML had an 8-year survival rate of less than 15%; current age-adjusted date rate with the introduction of TKI is at 0.3 per 100,000 per men and women per year.  

In Asia, CML is noted to have a lower incidence (mean of 0.8) than in Western countries but affecting a younger population with a median age of onset <50 years old. Based on surveys done, CML incidence (annual per 100,000 population) in the following Asian countries: China (0.4), Japan (0.9), Philippines (0.7-0.9), Singapore (0.7), South Korea (0.8), Taiwan (0.9), and Thailand (0.5). 

Pathophysiology

Chronic myeloid leukemia is a clonal myeloproliferative disorder characterized by the presence of the balanced genetic translocation of chromosomes 22 and 9, the Ph chromosome. The ABL1 gene encodes a non-receptor tyrosine kinase on chromosome 9, while BCR is a breakpoint cluster region on chromosome 22. The resulting fusion oncogene encodes an oncoprotein that is constitutively active tyrosine kinase, which in turn activates a number of signal-transduction pathways, impacting the growth and survival of hematopoietic cells.

Risk Factors

The only known risk factor for CML is exposure to ionizing radiation.

Chronic Myeloid Leukemia_Disease Background

Classification

PHASES OF CML  

Chronic Phase (CP)  

Chronic phase, sometimes referred to as chronic stable phase, is a phase that is easily controlled by oral agents. It is defined as <10% blasts in the peripheral blood and the bone marrow.  

Advanced Phase  

Accelerated Phase (AP)  

Criteria for defining AP by the World Health Organization (WHO) (≥1 of the following):

• 10-19% blasts in the peripheral blood smear (PBS) or in the nucleated bone marrow cells
• ≥20% basophils in the peripheral blood
• Persistent thrombocytopenia (<100,000/µL platelets) that is unrelated to therapy
• Persistent thrombocytosis (>1,000,000/µL platelets) that is unresponsive to therapy
• Progressive splenomegaly and increased white cell count (>10 x 10⁹/L) that is unresponsive to therapy
• Cytogenic evolution (chromosomal abnormalities other than Ph chromosome during therapy)
• Hematologic resistance to first-line TKI therapy
• Hematologic, cytogenetic, or molecular indications of resistance to two sequential TKIs
• ≥2 mutations in BCR::ABL1 during TKI therapy

Modified criteria used at MD Anderson Cancer Center (MDACC)

• ≥15% and <30% peripheral blood blasts
• ≥30% combined peripheral blood blasts and promyelocytes
• ≥20% peripheral blood basophils
• ≤100 x 109/L platelet count unrelated to therapy
• Clonal evolution in Ph+ cells

Blast Phase (BP)  

In the blast phase, disease progression may occur in patients without a preceding AP-CML and are refractory to treatment.  

The criteria for defining BP by the WHO are the following:

• ≥20% blasts in the PBS or bone marrow blasts
• Presence of large foci or clusters of blasts in the bone marrow biopsy
• Presence of extramedullary blast infiltrates

The criteria used by the International Bone Marrow Transplant Registry are the following:

• Myeloid BP-CML
  • ≥30% blasts in the blood, marrow, or both
  • Presence of extramedullary infiltrates of leukemic cells
• Lymphoid BP-CML
  • Any increase in lymphoblasts in the peripheral blood or bone marrow