Chronic Myeloid Leukemia: causes, risk factors, genetics, diagnoses, and treatment


  • The diagnosis and presentation in 50% cases is an incidental finding in routine laboratory tests.
  • It is estimated that fewer than 6,500 new cases per year are diagnosed.
  • The overall 5-year relative survival rates are 65.9%

Chronic myelogenous leukemia is a type of cancers of the blood cells or Cancer of white blood cells or lymphocytes (leukemia) and normally starts in the bone marrow cells and then invades the blood.  It is very slowly progressive disease characterized by an excess of white blood cells produced by the bone marrow myeloid cells; biologically, cancer producing myeloid cells can transform into red blood cells, white blood cells, and platelets.  The term “chronic” in chronic myelogenous leukemia implies that this cancer tends to progress more slowly than acute forms of leukemia; and “myelogenous” in chronic myelogenous leukemia indicates the origin of the cancer cells, the myeloid cells

Philadelfia chromosome

It is estimated that fewer than 6,500 new cases per year are diagnosed.  Chronic myelogenous leukemia typically affects older adults and rarely in children, though it can affect any age, The median age of presentation is between 45-55 years of age, it increases with age.  Up to 30% of patients are older than 60 years. Males are slightly more affected than females; male-to-female ratio-1.3:1.

The diagnosis and presentation in 50% cases is an incidental finding in routine laboratory tests. 85% of cases are diagnosed during the chronic phase. At diagnosis, most patients, have a white blood count (the number of white blood cells circulating in the blood) increased above normal.


The overall 5-year relative survival rates are 65.9%, The biological course of CML is divided into Chronic phase and advance phases–which is Subdivided into accelerated phase and blast crisis. The median duration of the chronic phase is 5-6years; the accelerated phase is 6-9 months; the blast crisis is about 3-6 months.
Of the, approximately 63,000 cases of leukemia diagnosis yearly, chronic myeloid leukemia accounts for 15-20% of all leukemias.


What are the causes of chronic myelogenous leukemia?

Today, the cause of chronic myeloid leukemia (CML) is known to result from a specific genetic abnormality, which occurs, in the blood stem cell. Some of them include:

-Genetic mutations:  Most of the molecular genetic changes associated with chronic myelogenous leukemia and the detection of Philadelphia chromosome (22 q-) goes back to 1960.  Follow-up 1973 by the identification of the reciprocal translocation-involving chromosome 9 and 22. Approximately 95% of those suffering from CML harbor this abnormality. The Ph chromosome results from a translocation of genes located on the long arms of chromosomes 9 and 22.  In 1980, the discovery of the unique fusion gene term BCR ABL gave us a better understanding. Single stem cell with the ability to multiply acquires the   Philadelphia chromosome carrying the BCL–ABL fusion that offers cells a proliferative advantage. These cells secreted surviving and growth factors like STATs, NFK, interleukin-3, G-CSF, etc. The transformation from the chronic phase to the last phase is associated with additional molecular changes.

-heavy radiation exposure.

Pesticides or Benzenes exposure as part of their work seem to have a moderately increased risk of developing CML.


What are the symptoms of CML?

50% of patients with CML are diagnosed during a routine laboratory test or after seeking medical care due to lack of energy and fatigue from:

– Anemia

– Bleeding from the nose or gums, petechia (red spots are seen on the skin commonly over the shins and ankles), and purpura (groups of petechiae resulting in larger red skin spots).

– Abdominal pain or discomfort

– Bruising from insufficient platelets

– Enlargement of the spleen leading to abdominal and left chest and shoulder discomfort

–Satiety, which is the inability to eat meals

– Changes in bowel patterns.


-Shortness of breath

-Bone pain.

How is Chronic Myelogenous leukemia diagnosed?

Diagnosis is a microscopic analysis of the peripheral blood from his CML patient and this will reveal the following:
-An elevated number of granulocytes specially basophils and eosinophils

–The analyzed blood smear will also typically revealed immature myeloid cells.
– Bone marrow biopsy is for the diagnosis.  This includes the types and morphology of the bone marrow components bodies also used to delineate abnormalities in cytogenetics. additional studies like flow cytometry, mutations, biological markers, and fluorescence in situ hybridization (FISH).
–Detection of the Philadelphia chromosome.
– molecular evidence of the translocation is not detected the condition is better characterized as a myeloproliferative disorder or undifferentiated myelodysplastic disorder.  In these cases is the biological clinical course is different from a patient with CML

 How is chronic myelogenous leukemia treated?

Before any treatment is rendered, multiple factors need to be considered including personal medical history, clinical examination typing for bone marrow.  Prior to targeted immunotherapy, the first line of therapy was more marked patient.  But now bone marrow transplantation is reserved for those who failed to respond to targeted immune therapy. .Bone marrow transplant involves using the healthy bone marrow cells of someone else to replace the patient’s own, cancerous bone marrow. To prevent the donor’s immune system from damaging the patient’s body (a condition known as graft-versus-host disease), tissue typing must be performed to determine if a donor and a patient ‘match’. This is determined by the level of resemblance of specific proteins called Human Leukocyte Antigen (HLA), between the patient and donor. Since the process of finding a matching bone marrow may take a few months, it is helpful to know the patient’s type ahead of time. HLA typing of the sisters or brothers who are possible donors should also be performed. If siblings do not ‘match’, unrelated donors will be screened.

Phases of CML

Like many other cancers, Staging is fundamental for prognosis and risk classification. The stage of the disease is determined by the “phase including chronic, accelerated, and blastic phase or blast crisis.

Multiple scoring systems using patients and disease characteristics have been developed which provide an estimate of the likelihood of response to therapy and survival. When using the most up to date, Scoring System, five-year, progression-free survival was significantly better in the low than in the high-risk group (90% vs. 82%)

The aforementioned t(9;22) mutation results in the mutation of a tyrosine kinase. Today, all patients should first be treated with an inhibitor of this mutated tyrosine kinase. Other agents, including interferon and hydroxyurea, have a limited role in first-line therapy. Hydroxyurea is used to rapidly lower disease burden and white blood cell counts. Imatinib is a first generation oral, tyrosine kinase inhibitor which achieves an 8-year overall survival of nearly 90% of patients. Second generation tyrosine kinase inhibitors, such as dasatinib or nilotinib, may also be considered for all patients with CML at diagnosis.

Response assessment is based on 3 levels of response: hematologic response, cytogenetic response, and molecular response, as described below.  The hematologic assessment of hematologic response should be performed after the initiation of therapy every 2 weeks to monitor peripheral white blood cell (WBC) and platelet counts. A complete hematologic response (CHR) is the association of a total WBC <10×109 /l, a WBC formula with no present immature granulocytes and <5% of basophils, platelets count <450×109 /l.  Cytogenetic response (CgR)  o Cytogenetics should be monitored after 3 months, 6 months, 12 months, and 18 months of therapy with a tyrosine kinase inhibitor. Until a complete cytogenetic response (CCgR) is achieved, cytogenetics should be repeated at least every 6 months.  A complete cytogenetic response (CCgR) is defined by the inability to detect the Philadelphia chromosome by analyzing the chromosomes metaphases o A partial cytogenetic response (PCgR) is defined as the presence of 1%–35% positive Philadelphia chromosome metaphases. Molecular response* o Monitoring of molecular response is done with PCR which quantifies the BCRABL/ABL anomalies o It should be repeated at least every 3 months until a major molecular remission is achieved o Major molecular remission is defined by a PCR result with BCR-ABL/ABL <0.10% on the International Scale.  Once both a complete cytogenetic response and a major molecular remission have been achieved, cytogenetic monitoring should be performed every 12 months and molecular monitoring by PCR should be performed every 6 months. Patients who achieve an optimal response should continue therapy with Imatinib or the second generation tyrosine kinase inhibitor they are currently receiving. This group of patients should only discontinue therapy in the setting of a clinical trial. Patients with only a suboptimal response can be considered for a dose increase in their current tyrosine kinase inhibitor or a change of therapy, if they are receiving Imatinib, to a second-generation tyrosine kinase inhibitor. In patients failing to respond to imatinib, the treatment should be changed to a second-generation tyrosine kinase inhibitor such as dasatinib or nilotinib.

Targeted therapies

Treatment for accelerated phase or blast crisis CML In these phases, the evidence is more limited to decide which treatment option is the best. Treatment with a tyrosine kinase inhibitor can be initiated in patients who have not already been treated with a tyrosine kinase inhibitor. Change to another tyrosine kinase inhibitor or chemotherapy can be considered for patients who have already been treated with a tyrosine kinase inhibitor. However, those options are effective for only a limited time. In these patients, performing an allogeneic bone marrow transplant remains the most valid option and should be considered. This is the process of transferring someone else’s bone marrow stem cells\ into the patient. The patient’s white blood cells, red blood cells, and platelets are replaced by the donor’s cells. The donor’s cells will all become part of the patient’s own blood.

The resistant disease can develop as the patient’s disease progresses resulting from mutations* in the BCR-ABL* tyrosine kinase. It is important when the disease progresses and therapy is either increased in dosage or changed to a different tyrosine kinase inhibitor, that mutations which lead to resistance to therapy with a tyrosine kinase are screened.


The information in this document does not replace a medical consultation. It is for personal guidance use only. We recommend that patients ask their doctors about what tests or types of treatments are needed for their type and stage of the disease.


  • American Cancer Society
  • The National Cancer Institute
  • National Comprehensive Cancer Network
  • American Academy of Gastroenterology
  • National Institute of Health
  • MD Anderson Cancer Center
  • Memorial Sloan Kettering Cancer Center
  • American Academy of Hematology

© Copyright 2018 - Hematology Oncology Care. Digital Marketing by MD Digitas