Initial Diagnosis

Cytogenetics serves to identify the presence of the t(9;22) translocation in only approximately 95% of cases of CML

but can identify the presence of other chromosomal abnormalities. In one half of the patients with a normal kary-otype, the BCR-ABL1 fusion transcript is detectable at the molecular level. This discrepancy is due to a submicro-scopic genetic fusion. Therefore, in those patients with a normal karyotype, who have the clinical and hematologi-cal profile of CML, molecular testing serves a primary role in CML diagnosis. In the remaining patients, who are negative for both the Philadelphia chromosome and the BCR-ABL1 fusion transcript, alternative diagnoses such as atypical CML or chronic myelomonocytic leukemia should be considered (Figure 35-3).

Cytogenetics

^PS^Hj ~95% Positive

~5% Negative

Molecular testing

j^SfcsjwH ~2.5% Positive Not CML ~2.5% Negative

Figure 35-3. Broad diagnostic algorithm for the utilization of cytogenetic and molecular testing in the initial diagnosis of CML,highlighting the complementary roles of these technologies. Even if cytogenetic analysis is positive, molecular testing is required to determine the molecular target for therapy and monitoring.

Figure 35-3. Broad diagnostic algorithm for the utilization of cytogenetic and molecular testing in the initial diagnosis of CML,highlighting the complementary roles of these technologies. Even if cytogenetic analysis is positive, molecular testing is required to determine the molecular target for therapy and monitoring.

Molecular testing serves to document the presence of BCR-ABL1 fusion transcripts at diagnosis, both for the rational use of targeted therapy (imatinib mesylate and newer agents) and for subsequent molecular monitoring. Indeed, once the initial diagnosis of CML is established, periodic monitoring of both the therapeutic response and the level of residual disease becomes critical to evaluation and therapeutic decision-making.

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