Chronic myeloid leukemia (CML) accounts for 2‐3% of leukemias in children under 15 and 9% in adolescents aged 15‐19. The diagnosis and management of CML in children, adolescents, and young adults have several differences compared to that in adults. This review outlines the diagnosis and management of the underlying disease as well as challenges that can occur when dealing with CML in this patient population.

BACKGROUND: Flow cytometry (FC) is a commonly requested test in the workup of leukocytosis in community practices. The role of FC in chronic-phase chronic myeloid leukemia (CP-CML) is unknown. We hypothesized that finding aberrant cells with FC in CP-CML may predict early blast-phase (BP) transformation. METHODS: Results for FC performed at the time of diagnosis for adult and pediatric patients with CP-CML who were referred to our institution were reviewed, and they were correlated with outcomes. RESULTS: FC was performed at the time of diagnosis for 110 of 233 patients (47%) with CP-CML. Aberrant populations, representing a median of 2% (range, 0.3%-15%), were detected with FC in 30% of patients (33 of 110): 2 of these 33 patients expressed lymphoid markers, and 31 expressed aberrant myeloid markers. Patients received imatinib (85%), dasatinib (12%), or nilotinib (3%) as their first-line treatment. With a median follow-up of 43 months (range, 2-113 months), chronic myeloid leukemia transformed to BP in 5 of the 33 patients. The 2 patients with lymphoid markers and 3 of the 31 patients with aberrant myeloid markers experienced a transformation to lymphoid BP at a median of 11 months (range, 4-72 months) after the initiation of tyrosine kinase inhibitor therapy. Although both cases with detectable lymphoid markers rapidly progressed to lymphoid BP, the positive predictive value of BP transformation by the detection of myeloid aberrant cells with FC was only 10% (3 of 31). CONCLUSIONS: In contrast to aberrant myeloid markers, the detection of lymphoid markers by FC at the time of the diagnosis of CP-CML appears to be associated with early progression to lymphoid BP. Cancer 2015;121:872-5.

TsAF8 is a temperature-sensitive (TS) mutant of BHK21 cells that arrests at nonpermissive temperatures in the mid-G1 phase of the cell cycle. TsAmaR-1 is a TS for growth mutant of CHO cells with a Ts- and alpha-amanitin-resistant (AmaR) RNA polymerase II activity. Hybrid TsAmaR-1 x TsAF8 cell lines were constructed at permissive temperatures. Such hybrid cells did not grow at nonpermissive temperatures; the two TS mutations did not complement. Two different AmaR derivatives of TsAF8 were isolated. Each contained only AmaR polymerase II activity, indicating that this RNA polymerase II gene locus in TsAF8 is functionally hemizygous, as would be expected for a locus in which the recessive TsAF8 mutation had occurred. One of these AmaR isolates of TsAF8 had at. Two different AmaR derivatives of TsAF8 were isolated. Each contained only AmaR polymerase II activity, indicating that this RNA polymerase II gene locus in TsAF8 is functionally hemizygous, as would be expected for a locus in which the recessive TsAF8 mutation had occurred. One of these AmaR isolates of TsAF8 had a partially reverted TS+ phenotype. Taken together these results suggest that the TS mutation in TsAF8 is in RNA polymerase II.