Chronic myeloid leukemia (CML) is a form of leukemia characterized

by the increased and unregulated growth of predominantly myeloid cells

in the bone marrow and the accumulation of these cells in the blood.
CML is a clonal bone marrow stem cell disorder in which proliferation of
mature granulocytes (neutrophils, eosinophils, and basophils) and their
precursors is the main finding. It is a type of myeloproliferative disease
associated with a characteristic chromosomal translocation called the
Philadelphia chromosome.

Signs and symptoms

 asymptomatic
 gout
 increased susceptibility to infections,
 anemia
 easy bruising
 Splenomegaly may also be seen.

Diagnosis

1. CML is often suspected on the basis on the complete blood count,

which shows increased granulocytes of all types, typically
including mature myeloid cells.
2. Basophils and eosinophils are almost universally increased;
3. bone marrow biopsy is often performed as part of the evaluation
for CML,
4. Ultimately, CML is diagnosed by detecting the Philadelphia
chromosome. This characteristic chromosomal abnormality can be
detected by routine cytogenetics, by fluorescent in situ
hybridization, or by PCR for the bcr-abl fusion gene

Pathophysiology

CML was the first malignancy to be linked to a clear genetic abnormality,

the chromosomal translocation known as the Philadelphia chromosome.
In this translocation, parts of two chromosomes (the 9th and 22nd by
conventional karyotypic numbering) switch places. As a result, part of the
BCR ("breakpoint cluster region") gene from chromosome 22 is fused
with the ABL gene on chromosome 9. This abnormal "fusion" gene

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generates a protein of p210 or sometimes p185 weight (p is a weight
measure of cellular proteins in kDa). Because abl carries a domain that
can add phosphate groups to tyrosine residues (a tyrosine kinase), the bcr-
abl fusion gene product is also a tyrosine kinase.

The fused bcr-abl protein interacts with the interleukin 3beta(c) receptor
subunit. The bcr-abl transcript is continuously active and does not require
activation by other cellular messaging proteins. In turn, bcr-abl activates a
cascade of proteins which control the cell cycle, speeding up cell
division. Moreover, the bcr-abl protein inhibits DNA repair, causing
genomic instability and making the cell more susceptible to developing
further genetic abnormalities. The action of the bcr-abl protein is the
pathophysiologic cause of chronic myelogenous leukemia.

Chronic phase

Approximately 85% of patients with CML are in the chronic phase at the
time of diagnosis. During this phase, patients are usually asymptomatic or
have only mild symptoms of fatigue or abdominal fullness. Ultimately, in
the absence of curative treatment, the disease progresses to an accelerated
phase.

Accelerated phase

The WHO criteria are perhaps most widely used, and include:

 10–19% myeloblasts in the blood or bone marrow

 >20% basophils in the blood or bone marrow
 Platelet count <100,000, unrelated to therapy
 Platelet count >1,000,000, unresponsive to therapy
 Cytogenetic evolution with new abnormalities in addition to the
Philadelphia chromosome
 Increasing splenomegaly or white blood cell count, unresponsive to
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.

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Blast crisis

Blast crisis is the final phase in the evolution of CML, 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 CML:

 >20% myeloblasts or lymphoblasts in the blood or bone marrow

 Large clusters of blasts in the bone marrow on biopsy
 Development of a chloroma (solid focus of leukemia outside the
bone marrow)

Chronic lymphocytic leukemia (also known as "chronic lymphoid

leukemia" or "CLL"),

CLL affects a particular lymphocyte, the B cell, which originates in the

bone marrow, develops in the lymph nodes, and normally fights infection.
In CLL, the DNA of a B cell is damaged, so that it can't fight infection,
but it grows out of control and crowds out the healthy blood cells that can
fight infection.

CLL is an abnormal neoplastic proliferation of B cells. The cells

accumulate mainly in the bone marrow and blood. Although not
originally appreciated, CLL is now felt to be identical to a disease called
small lymphocytic lymphoma (SLL), a type of non-Hodgkin's lymphoma
which presents primarily in the lymph nodes. The World Health
Organization considers CLL and SLL to be "one disease at different
stages, not two separate entities".

CLL is a disease of adults. Most (>75%) people newly diagnosed with

CLL are over the age 50, and the majority are men.

Most people are diagnosed without symptoms as the result of a routine

blood test that returns a high white blood cell count,

as it advances CLL results in swollen lymph nodes, spleen, and liver, and
eventually anemia and infections. Early CLL is not treated, and late CLL
is treated with chemotherapy and monoclonal antibodies.

Survival varies from 5 years to more than 25 years.

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Symptoms and signs

1. Most people are diagnosed without symptoms as the result of a

routine blood test that returns a high white blood cell count
2. Uncommonly, CLL presents as enlargement of the lymph nodes
without a high white blood cell count or no evidence of the disease
in the blood. This is referred to as small lymphocytic lymphoma. In
some individuals the disease comes to light only after the
neoplastic cells overwhelm the bone marrow resulting in anemia
producing tiredness or weakness.

Diagnosis

CLL is usually first suspected by the presence of a lymphocytosis, an

increase in one type of the white blood cell, on a complete blood count
(CBC) test.

Most often the lymphocyte count is greater than 4000 cells per mm3
(microliter) of blood but can be much higher.

This atypical molecular pattern includes the co-expression of cells

surface markers cluster of differentiation 5 (CD5) and cluster of
differentiation 23 (CD23).

All the CLL cells within one individual are clonal, that is genetically
identical. In practice, this is inferred by the detection of only one of the
mutually exclusive antibody light chains, kappa or lambda, on the entire
population of the abnormal B cells.

In CLL, the lymphocytes are genetically clonal, of the B cell lineage

(express marker molecules cluster of differentiation 19 (CD19) and
CD20), and characteristically express the marker molecules CD5 and
CD23. Morphologically, the cells resemble normal lymphocytes under
the microscope, although slightly larger, and are fragile when smeared
onto a glass slide giving rise to many broken cells (smudge cells).