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.
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)
Modified criteria used at
MD Anderson Cancer Center (MDACC)
- ≥15% and <30% peripheral blood myeloblasts
- ≥30% combined peripheral blood myeloblasts and promyelocytes
- ≥20% peripheral blood basophils
- ≤100 x 109/L platelet count unrelated to therapy
- Clonal evolution in Ph+ cells
- Absence of aberrant lymphoblasts in peripheral blood or bone marrow
- Aberrant lymphoblasts indicate BP-CML, although low-level aberrant lymphoblasts may be better classified as AP-CML due to their more indolent clinical behavior
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 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
- Presence of any aberrant lymphoblasts in the peripheral blood or bone marrow