Carcinoma in Situ


Chronic myeloid leukemia (CML) is the abnormal growth of relatively mature myeloid (white blood) cells. Half of all patients with CML are diagnosed after the age of 67.

CML is associated with a chromosomal abnormality in which genetic material from chromosome 9 is transferred to chromosome 22. The chromosome containing the genetic switch is called the Philadelphia chromosome; this chromosome plays a role in the development of CML.

The exchange of genetic information that produces the Philadelphia chromosome  brings together two genes: the BCR (breakpoint cluster region) gene on chromosome 22 and the ABL (Ableson leukemia virus) gene on chromosome 9.  The combination of these two genes into the single BCR-ABL gene results in the production of a protein that contributes to uncontrolled cell growth.

Initially in CML, there is a gradual increase in mature, abnormal myeloid cells in the bone marrow. These cells eventually spill into the blood and other organs, causing symptoms such as fatigue from anemia or an enlarged spleen. The increase in leukemic cell numbers occurs slowly at first and is referred to as the chronic phase, but these cells invariably begin to increase more rapidly and/or include less mature cells, resulting in the accelerated or blastic phase. In order to understand the best treatment options available for chronic myeloid leukemia, it is important to know the phase of leukemia, since all new treatment information concerning chronic myeloid leukemia is categorized and discussed by the phase of disease.

Measuring Response to Treatment

Initial response to therapy is indicated by normalization of the peripheral blood counts (white blood cells, platelets and red blood cells) and return of increased bone marrow cellularity to normal. Most patients are followed with peripheral blood tests rather than repeated bone marrow examination. Cells collected from the bone marrow or peripheral blood will contain the Philadelphia chromosome, and cytogenetic tests (tests that detect chromosomal abnormalities) are used to monitor response to therapy. Currently the majority of newly diagnosed patients with CML will achieve a complete cytogenetic remission (no evidence of Philadelphia chromosome-positive cells).  More importantly, in patients with a complete cytogenetic remission a test called polymerase chain reaction (PCR) can determine the completeness of a “molecular” remission by measuring the presence of the BCR-ABL gene. As a general rule, the greater the degree of molecular response the longer the survival of an individual patient.

Staging of Chronic Myeloid Leukemia

Chronic Phase: Patients in the chronic phase of CML have stable disease with only minor symptoms, no cancer outside the bone marrow or spleen and white blood cell and platelet blood counts that are usually greater than normal.

Accelerated Phase: When chronic myeloid leukemia is difficult to control with Gleevec® (imatinib) or other therapies, the white blood count begins to increase. New symptoms may appear and old symptoms may worsen. The spleen may enlarge and/or new abnormal chromosomes can be detected in the bone marrow cells. Eventually, the leukemia becomes completely resistant to treatment and the bone marrow becomes overburdened with large numbers of immature white blood cells known as “blasts”. A diagnosis of accelerated phase requires at least one of the following:

  • The persistent presence of 10-30% myeloblasts in the bone marrow or peripheral blood.
  • A major increase of the white blood cell count to over 50,000, platelet counts that are increased or decreased and red blood cell levels that are low despite treatment.
  • Progressive enlargement of the spleen.
  • Growth of leukemia outside the bone marrow or spleen.
  • The presence of any cytogenetic abnormality in addition to a Philadelphia chromosome.
  • Persistent unexplained fever or bone pain.