The t922 Translocation

The Philadelphia (Ph) chromosome, a cytogenetic abnormality that is characterized by deletion or translocation of 22q11, was first described in cases of chronic myeloid leukemia (CML),but is now known to occur in 2 to 5 percent of all cases of childhood and 16 to 25 percent of adult ALL.31,32 In ALL the Ph chromosome arises most often through a t(9;22), with translocation of the c-abl protooncogene on chromosome 9 to either of two breakpoint regions within the BCR gene on chromosome 22, which results in production of either a 210-kd or 190-kd fusion protein with tyrosine kinase activity. Presence of a Ph chromosome appears to be an adverse risk factor for both children and adults with ALL33,34 despite the fact that it is associated with unfavorable presenting features, such as high leukocyte count, older age, organomegaly, and FAB L2 morphology. Almost all cases had immature B-progenitor (CD10+ CD19+ CD34+) immunophenotype. Myeloid markers were present in 24 to 65 percent of Ph+ ALL cases.35,36 Patients with Ph+ ALL are considered as suitable candidates for innovative and intensified strategies.37

The t(4;11) Translocation

The MLL gene, located at chromosome 11, band q23 is frequently disrupted by a variety of chromosomal rearrangements that occur in ALL and in a subset of de novo and secondary AMLs. The most common translocation involving 11q23 is translocation t(4;11)(q21;q23).38 It is observed in more than 60 percent of infants with ALL, 2 percent of children with ALL, and 3 to 6 percent of adults with ALL.35 It is invariably associated with young age (under 2 years), female sex, high white blood cell (WBC) counts, organomegaly, and CNS involvement.39-41 The morphology of the blasts can be either L1 or L2. Immunophenotype is of the early pre-B or pre-B-cell type with rearrangements of the Ig heavy chain (IgH) genes and is variably CD10-. Blast cells frequently express myeloid (CDw65, CD15) antigens. These observations suggest that the cell of origin in these leukemias is an early B-cell progenitor with the capacity to differentiate both lymphoid and myeloid lineages.34 The clinical outcome for both adults and children with the t(4;11) translocation is poor.34,39

The t(1;19) Translocation

This translocation results in the E2A/PBX fusion. A strong association exists between t(1;19) and pre-B-ALL especially in children,42 where the translocation is present in 25 to 30 percent of cases.34,43 Presence of t(1;19) identifies a subgroup of pre-B-cell ALL patients who are at risk for early relapse with standard therapy.44,45 However, it has been reported that patients with unbalanced der(19)t(1;19) translocations had significantly improved outcomes compared with those with balanced t(1;19).46

The t(12;21) Translocation

Before the availability of molecular methods such as fluorescent in situ hybridization (FISH) and reverse transcriptase polymerase chain reaction (RT-PCR) to detect t(12;21), it was thought to be of no significant prognostic value. However, in several studies the application of these molecular techniques have shown TEL/AML1 fusion transcripts in up to 27 percent of children with B-lineage ALL. Thus it becomes the most common fusion gene in pediatric ALL.47-50 The TEL/AML1 rearrangement conferred an exceptionally good outcome in childhood B-precursor ALL and provided prognostic information independent of the risk factors at presentation.49,51,52

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