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MPO, myeloperoxidase.

MPO, myeloperoxidase.

applied to more frequent cases in which blasts simultaneously express 'myeloid'- and 'lymphoid'-associa-ted markers. For example, a proportion of ALL cases express CD13, CD33 and/or CD15. In most of these cases, the expression of an array of lymphoid-associated antigens and the rearrangement of Ig or TCR genes strongly indicate a lymphoid origin. In a proportion of AML cases, blasts may express 'lymphoid-associated' markers, such as TdT, CD7, CD19 and/or CD56. The myeloid affiliation of these cases is usually clear and they rarely represent a diagnostic problem.

A distinct group of cases (1-2% of acute leukemias) are undifferentiated morphologically and cytochemically, and show recurrent phenotypic features such as HLA-DR, TdT and CD34 positivity, and lack of myeloperoxidase, CD13, CD33, CD79, CD22, CD 19, CD3, glycophorin and CD61. These cases have been named 'acute undifferentiated leukemia'.

Antigen-receptor gene rearrangements and genotypic abnormalities Virtually all cases of B-lineage ALL have IgH gene rearrangements, while approximately half of the cases also show TCR8 and TCR7 gene rearrangements and one-third TCR(3 gene rearrangements. Virtually all T-ALL cases have TCR(3 and TCR7 gene rearrangements, and 70% of cases have

TCRS gene rearrangements, while IgH genes are rearranged in approximately 15% of cases. Rearrangements of the same genes in B- and T-lineage cells are not always identical. For example, TCR8 genes found in B-lineage ALL usually have short junctional regions (i.e. V82-D83 and D82-D83), in contrast to the dominant V81DJS1. rearrangements in T-ALL. IgH gene rearrangements in B-lineage ALL at diagnosis are often biclonal or oligoclonal. Moreover, investigators have found changes in the pattern of rearrangement at presentation and relapse for both IgH and TCR genes, an important potential pitfall when these genes are used to track residual leukemia (see below). Nevertheless, in the majority of cases, at least one major rearranged IgH, TCR7 or TCR8 allele appears to persist from diagnosis to relapse. Oligoclonality and clonal evolution in IgH genes are often due to disruption in the V-N-D portion, while the D-N-J sequence is left unmodified. Rearrangements of the IgH and/or TCR genes can also occur in approximately 10% of AML.

Some of the most common genotypic abnormalities of acute leukemia are summarized in Table 3. In approximately 25-40% of cases of adult ALL and 3-5% of cases of childhood ALL, leukemic cells have a reciprocal translocation between chromosomes 9q34 and 22qll (Philadelphia (Ph)-chromosome),

Table 3 Some recurrent genotypic abnormalities in acute leukemia

Disease

Chromosomal abnormality

Molecular abnormality

Adults

Frequency (%)a Children

Acute lymphoblastic leukemia

t(9;22)(q34;q11)

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