Chronic myelogenous leukemia is a blood cancer that attacks the bone marrow as well. It is essentially a condition when there is accumulation of white blood cells (granulocytes) in the bone marrow. Abnormal white blood cells which are usually designated as leukemia cells or blast cells are frequently the primary cause of leukemia diseases. Human chromosomes have different roles and their abnormality involves a random exchange of parts between chromosomes 9 and 22. Therefore this gene mutation results in the detection of the BCR-ABL1 fusion gene which codes for a protein that stimulates the cell to grow and divide most irregularly. The infection is usually gradual and normally the first signs are not manifest until the disease is in its advanced stage. 

The incidence of CML globally is 0.87 cases/100,000 people which is almost the same for all ages but the peak of it was at the age of 70 and older where it reached 1.52 cases/100,000 people of that age. Besides that the disease higher chance of happening in males compared to females. The statistical centre of age at diagnosis is 56 years. 

Philadelphia Chromosome Formation: The chromosome 9 and 22 were phased in over 95% of CML cases. This phenomenon is called the Philadelphia chromosome which is the cause for this genetic anomaly. As a result the BCR-ABL gene is made up.  

BCR-ABL Oncogene: The gene forms an abnormally active protein called “TYK2”, which causes a cell signalling pathway that stimulates the cell growth and survival activities. 

Abnormal Myeloid Cell Growth: By this oncogene’s intervention the normal myeloid cells and granulocytes‘ development into mature cells in the bone marrow is ceased and, in their place, the immature leukocytes rapidly proliferate resulting in a high white blood cell count. 

Inhibition of Differentiation and Apoptosis: The fusion of protein prevents myeloid cells from maturing and the buildup of immature cells. It is also responsible for cell death prevention and thus the persistence and multiplication of abnormal cells. 

Clinical Manifestations: Among the earliest symptoms are tiredness weight loss, fever and abdominal pain from enlarged spleen and the lowered ability to fight off infections because of impaired immunity. 

Chronic Myelogenous Leukaemia is a consequence of the cytogenetic abnormality called Philadelphia chromosome. This chromosome features a translocation between the distinct chromosomes 9 and 22 and by doing so it generates a fusion gene called BCR-ABL. This unusual gene produces a protein that acts to stimulate cell division without being able to prevent them from growing out of control and this is what leads to CML. 

Cytogenetic Abnormalities: Specific genetic perversities e.g. the Philadelphia chromosome play their roles in CML and different additional chromosomal abnormalities correlate with worse outcomes in CML.  

Blast Crisis Transformation: As to CML development a subsequent crisis may result in an increased number of immature cells (blasts). It shall be related to a worse outcome. 

Response to Treatment: Patient responses to the treatment and most importantly so with tyrosine kinase inhibitors is significantly important in determining the prognosis. 

Age group: Although people of any age might be affected by CML, adults are the ones who are often diagnosed with the disease with an average age of 64.  

General Appearance 

Skin assessment 

Lymph Nodes examination 

Spleen and Liver assessment 

Cardiovascular assessment 

Respiratory assessment 

Neurological Examination 

Cardiovascular disease 

Thrombosis 

Anemia 

Gastrointestinal symptoms 

Psychological distress 

Unintentional Weight Loss: People with CML may lose weight accidentally and without attempting to.  

Abdominal pain: CML patients may experience splenomegaly or enlarged spleen and less frequently hepatomegaly or enlarged liver which can cause pain or fullness in the belly. 

Fatigue: This is also the common symptoms associated with CML. 

Tyrosine kinase inhibitors: TKIs are essential for treating chronic myeloid leukemia because they work by blocking the BCR-ABL protein.
Allogeneic Stem Cell Transplantation: When a patient has advanced CML or is resistant to several TKIs stem cells from a healthy donor are used to replace the diseased bone marrow. 

Clinical Trials: For patients whose traditional treatments are unsuccessful or who would like access to innovative medications clinical trials investigate new CML treatments such as targeted therapy and therapeutic combinations. 

Hematology

Reduce Toxin Exposure: To reduce the burden on your immune system, stay away from pesticides and smoking.  

Keep It clean: To improve air quality and lower allergies keep your area neat and free of mould and dust. 

Handle Stress: Reduce stress which can impair your immune system by including calming methods like yoga or meditation. 

Remain Active: To improve your mood immunity and general well-being do light to moderate exercise daily. 

Hematology

Hydroxyurea: Hydroxyurea acts by blocking the ribonucleotide reductase enzyme which is useful in producing DNA. 

Busulfan: It acts as an alkylating agent which prevents the cell division and inhibits DNA synthesis.  

3- Role of Tyrosine Kinase Inhibitors in treating CML: Specialty: Hematology 

Imatinib: The first TKI authorised for the treatment of CML was imatinib. Particularly during the chronic stage of the illness it has proven to be quite successful.  

Bosutinib: Patients with CML who are resistant to, or intolerant of previous therapy may be treated with bosutinib a TKI. 

Hematology

Pemigatinib is a medication for adults with refractory/relapsed cholangiocarcinoma that inhibits FGFR 1/2/3 phosphorylation and reducing cell viability in cancer cell lines. 

Hematology

Diagnosis: CML is diagnosed through blood tests like CBC and bone marrow biopsy, often confirmed with molecular tests like PCR or FISH for the Ph chromosome. 

Initial treatment: It includes tyrosine kinase inhibitors such as imatinib, dasatinib and bosutinib. These are chosen based on factors like age and health to reduce abnormal white blood cells and halt disease progression.  

Monitoring: It involves regular tests like blood cell counts and quantitative PCR and occasionally bone marrow biopsies to track treatment response and disease progression. 

Long-Term Management: Patients with good treatment responses continue TKI therapy and undergo regular monitoring for disease recurrence or progression.