1Servicio de Genética. Hospital de Pediatría "Prof. Dr. J. P. Garrahan", Buenos Aires, Argentina.
2Servicio de Hemato-Oncología. Hospital de Pediatría "Prof. Dr. J. P. Garrahan", Buenos Aires, Argentina.
3Servicio de Inmunología. Hospital de Pediatría "Prof. Dr. J. P. Garrahan", Buenos Aires, Argentina.
However, the occurrence of t(16;21) in acute lymphoblastic leukemia (ALL) is very rare. To our knowledge, it has been reported in only 13 ALL patients, including 10 adults and three children [3, 4, 5, 6].
We herein describe the case of a 6-year-old boy who was admitted to our hospital owing to parotid enlargement and cranial nerve VII palsy. Physical examination revealed liver enlargement, and blood evaluation showed a white blood cell count of 6.1×109/L with 13% blasts, hemoglobin level of 10.9 g/dL, and platelet count of 190×109/L. A bone marrow aspirate showed that 81% of the cellularity was replaced by L1/L2 French-American-British morphology lymphoblasts (Fig. 1). Immunophenotyping of the blasts with flow cytometry using a FacSort instrument (Becton Dickinson, San José, CA, USA) indicated a common ALL (B II) according to the European Group for the Immunological Classification of Leukemias. The leukemic cells expressed CD79a, CD22, CD19, CD10, HLA-DR, and were partially positive for TdT, CD34, and CD117 while negative for cytoplasmic µ-chain.
Conventional cytogenetic analysis of the bone marrow cell culture revealed the following karyotype: 46,XY,t(16;21) (p11.2;q22)/46,XY (Fig. 2A). Subsequently, reverse transcriptase polymerase chain reaction (RT-PCR) and direct sequencing were performed to assess the presence of
The patient was enrolled in our current protocol for ALL-BFM ALL-IC 2009. His response to the prednisone pre-phase was good. He then underwent induction chemotherapy consisting of vincristine, daunorubicin, and L-asparaginase. The minimal residual disease (MRD), detected by flow cytometry of the bone marrow aspirate, at day 15 of treatment was 0.19%. The patient achieved complete remission after the induction phase and was stratified as an intermediate risk patient, with central nervous system involvement owing to facial palsy. However, blast cells were not detected in the cerebrospinal fluid at diagnosis. He received consolidation chemotherapy with cytarabine, cyclophosphamide, and mercaptopurine, followed by high-dose methotrexate. Subsequently, he received late re-induction therapy with dexamethasone, vincristine, doxorubicin, L-asparaginase, cyclophosphamide, cytarabine, and thiopurine, as well as maintenance therapy with mercaptopurine and methotrexate. He remained free of leukemia 31 months after diagnosis. Flow cytometry analysis of MRD was negative on day 33 (after the induction phase) and on week 12 (prior to the administration of the consolidation phase with high-dose methotrexate). MRD was also confirmed to be negative by quantitative real-time PCR at these time points (day 33 and week 12).
According to the Mitelman database and the literature, about 71 cases of t(16;21) have been reported to date, most of them in AML . The rearrangement of the two chromosomes involved in such a translocation forms the
In AML, four types of chimeric transcripts have been described, designated as types A, B, C, and D, which correspond to the 255-, 211-, 176-, and 349-bp chimeric products, respectively [2, 8]. These transcripts consist of
On the other hand, in ALL, a recent study of 256 adult patients reported that
In conclusion, the present case supports the possible association between ALL cases with t(16;21) and a specific type of