Chronic myeloid leukemia in a 4 years old female. Peripheral blood (MGG stain) Peripheral blood (MGG stain): marked leukocytosis with granulocyte left shift A small, hypolobated megakaryocyte (center of field) in a bone marrow aspirate, characteristic of chronic myeloid leukemia.<unk>  is often suspected on the basis of a complete blood count, which shows increased granulocytes of all types, typically including mature myeloid cells. Basophils and eosinophils are almost universally increased; this feature may help differentiate<unk>  from a leukemoid reaction. A bone marrow biopsy is often performed as part of the evaluation for<unk> , and<unk>  is diagnosed by cytogenetics that detects the translocation t(9;22)(q34;q11.2) which involves the ABL1 gene in chromosome 9 and the BCR gene in chromosome 22. As a result of this translocation, the chromosome looks smaller than its homologue chromosome, and this appearance is known as the Philadelphia chromosome chromosomal abnormality. Thus, this abnormality can be detected by routine cytogenetics, and the involved genes BCR-ABL1 can be detected by fluorescent in situ hybridization, as well as by PCR. Controversy exists over so-called Ph-negative<unk> , or cases of suspected<unk>  in which the Philadelphia chromosome cannot be detected. Many such patients in fact have complex chromosomal abnormalities that mask the (9;22) translocation, or have evidence of the translocation by FISH or RT-PCR in spite of normal routine karyotyping. The small subset of patients without detectable molecular evidence of BCR-ABL1 fusion may be better classified as having an undifferentiated myelodysplastic/myeloproliferative disorder, as their clinical course tends to be different from patients with<unk> .<unk>  must be distinguished from a leukemoid reaction, which can have a similar appearance on a blood smear. Classification<unk>  is often divided into three phases based on clinical characteristics and laboratory findings. In the absence of intervention,<unk>  typically begins in the chronic phase, and over the course of several years progresses to an accelerated phase and ultimately to a blast crisis. Blast crisis is the terminal phase of<unk>  and clinically behaves like an acute leukemia. Drug treatment will usually stop this progression if started early. One of the drivers of the progression from chronic phase through acceleration and blast crisis is the acquisition of new chromosomal abnormalities (in addition to the Philadelphia chromosome). Some patients may already be in the accelerated phase or blast crisis by the time they are diagnosed. Chronic phase Approximately 85% of patients with<unk>  are in the chronic phase at the time of diagnosis. During this phase, patients are usually asymptomatic or have only mild symptoms of fatigue, left side pain, joint and/or hip pain, or abdominal fullness. The duration of chronic phase is variable and depends on how early the disease was diagnosed as well as the therapies used. In the absence of treatment, the disease progresses to an accelerated phase. Precise patient staging based on clinical markers and personal genomic profile will likely prove beneficial in the assessment of disease history with respect to progression risk. Accelerated phase Criteria for diagnosing transition into the accelerated phase are somewhat variable; the most widely used criteria are those put forward by investigators at M.D. Anderson Cancer Center, by Sokal et al., and the World Health Organization. The WHO criteria are perhaps most widely used, and define the accelerated phase by the presence of ≥1 of the following haematological/cytogenetic criteria or provisional criteria concerning response to tyrosine kinase inhibitor (TKI) therapy *Haematological/cytogenetic criteria *Persistent or increasing high white blood cell count (> 10 × 109/L), unresponsive to therapy *Persistent or increasing splenomegaly, unresponsive to therapy *Persistent thrombocytosis (> 1000 × 109/L), unresponsive to therapy *Persistent thrombocytopenia (9/L), unrelated to therapy *≥ 20% basophils in the peripheral blood *10―19% blasts in the peripheral blood and/or bone marrow *Additional clonal chromosomal abnormalities in Philadelphia (Ph) chromosome-positive (Ph+) cells at diagnosis, including so-called major route abnormalities (a second Ph chromosome, trisomy 8, isochromosome 17q, trisomy 19), complex karyotype, and abnormalities of 3q26.2 *Any new clonal chromosomal abnormality in Ph+ cells that occurs during therapy *Provisional response-to-TKI criteria *Haematological resistance (or failure to achieve a complete haematological response d) to the first TKI *Any haematological, cytogenetic, or molecular indications of resistance to two sequential TKIs *Occurrence of two or more mutations in the BCR-ABL1 fusion gene during TKI therapy The patient is considered to be in the accelerated phase if any of the above are present. The accelerated phase is significant because it signals that the disease is progressing and transformation to blast crisis is imminent. Drug treatment often becomes less effective in the advanced stages. Blast crisis Blast crisis is the final phase in the evolution of<unk> , and behaves like an acute leukemia, with rapid progression and short survival. Blast crisis is diagnosed if any of the following are present in a patient with<unk> : *>20% blasts in the blood or bone marrow *The presence of an extramedullary proliferation of blasts
Chronic myelogenous leukemia
Acute myeloid leukemia
Chronic neutrophilic leukemia
Myeloid leukemia
Chronic lymphocytic leukemia
Acute monocytic leukemia
Prolymphocytic leukemia
Lymphoid leukemia