Chronic leukemias

Chronic myelogenous leukemia

Chronic myelogenous leukemia (CML) is a clonal proliferation of hematopoietic precursor cells, with a greatest incidence between 40 and 60 years of age. The t(9;22)(q34;qll), or Philadelphia (Ph)-chromo-some, and BCR-ABL rearrangements are characteristic of CML, and occur in all hematopoietic lineages, an indication that the disease originates from a multipotent progenitor cell. Rare cases of CML (<5%) are Ph-negative but in many of these cases (BCR-ABL) rearrangements can be detected with molecular techniques. PCR amplification of BCR-ABL can be used to detect disease recurrence after allogeneic bone marrow transplantation, although positive PCR results have not consistently predicted treatment outcome.

At diagnosis, CML usually features extremely high white blood cell counts (e.g. >100xl09/l); most cells are granulocytes or maturing myeloid forms. This morphologic appearance is typical of the initial phase of the disease ('chronic phase'). However, it is not stable and invariably transforms into a 'blast crisis', where the bulk of the neoplastic population is represented by immature-looking forms, resembling those seen in acute leukemias. In the majority of patients, these blasts have morphological and pheno-typical features identical to those seen in AML, while approximately 30% of cases have lymphoid morphology and B-lineage ALL immunophenotype; T cell blast crises are rare.

Chronic lymphoid leukemias

B-chronic lymphocytic leukemia (B-CLL) is the most common chronic lymphoid leukemia, and accounts for about 30% of all leukemia patients diagnosed in the Western world, but is less frequent in the Orient. B-CLL is a disease of the elderly, unusual under the age of 40. The most consistent chromosomal abnormality is trisomy of the chromosome 12. Patients with a normal karyotype appear to do better than those with chromosomal abnormalities, and multiple chromosomal abnormalities are associated with a more rapid progression of the disease. Leukemic cells in B-CLL and in other B-lineage chronic lymphoid leukemias (i.e. hairy cell leukemia (HCL), and prolymphocyte leukemia (PLL)) typically express CD 19, CD79, CD20 and CD37, whereas TdT is absent (Table 4). In B-CLL, the level of Ig expression on the cell membrane is heterogeneous and often weak. Similarly, membrane expression of CD22 may be extremely weak or undetectable. CD23 and CD5 expression are also characteristic of B-CLL while CD25 and CD 11c expression together with high-level expression of CD22 are typical of HCL (Table 4). CD5 expression in B-CLL recalls the phenotype of cells found in primary follicles of fetal lymph nodes and spleen, possibly equivalent to murine Lyl+ B cells.

Typical cell markers of T cell chronic lymphoid

Table 4 Predominant immunophenotypes of chronic B cell leukemias


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