Pediatric chronic myeloid leukemia with inv(3)(q21q26.2) and T lymphoblastic transformation: a case report

Abstract

BackgroundChronic myeloid leukemia (CML) comprises ~3 % of pediatric leukemia. Although therapy with tyrosine kinase inhibitors (TKIs) is highly effective for CML, multiple factors have been identified as predictive of treatment failure. Chromosomal abnormalities involving the MECOM locus at 3q26 portend therapy resistant disease in adults, yet have never been described in pediatric patients and have not been associated with T lymphoblastic progression.Case presentationWe present a case of an 11-year-old boy with CML possessing the unique combination of T lymphoblastic transformation and a subclone harboring inv(3)(q21q26.2) at diagnosis. This is the first reported case of pediatric CML with inv(3)(q21q26.2) and the first case of T lymphoblastic progression associated with this karyotype. The patient was treated with single agent TKI therapy with robust initial response. Marrow histology at one month showed restoration of trilineage hematopoiesis and BCR-ABL RT-PCR at three months showed a 1.4 log reduction in transcript levels.ConclusionsThe karyotypic abnormality of inv(3)(q21q26.2) in CML is not restricted to adult patients. Moreover, while chromosome 3 abnormalities are markers of TKI resistance in adults, our patient showed a robust early response to single agent TKI therapy. This finding suggests pediatric CML with inv(3)(q21q26.2) may have distinct features and more favorable treatment responses than those described in adults.

The acquisition of molecular drivers in pediatric therapy-related myeloid neoplasms

“…3e ). Similar MECOM protein expression was detected in the other MECOM altered cases 51 , but not in tMN cases without a MECOM SV (Fig. 3e ).…”

BCR-ABL1 positive AML or CML in blast crisis? A pediatric case report with inv(3) and t(9;22) in the initial clone

“…The inv(3) in our patient represents the class II-mutation and the t(9;22) constitutes the class I-mutation. The oncogenic transcription factor MECOM ( EVI1 ) is located on 3q26 and plays an essential role in hematopoietic stem cell renewal and differentiation [13] . An inv(3) results in overexpression of MECOM ( EVI1 ), which leads to growth inhibition and differentiation of cells in AML patients [19] .…”

Chronic myeloid leukemia in childhood: a case report

“…The use of these agents has vastly improved prognosis; however, a subset of patients progress to AP or BP despite adequate treatment, and the prognosis for CML-BP remains poor. 6 There are significant differences in pediatric and adult CML. Biologically, in adult CML, there is a single breakpoint cluster within the first centromeric 1.5 kb of the BCR, whereas, in pediatric CML, there is a bimodal breakpoint distribution which is similar to adult Ph+ acute lymphoblastic leukemia with M-BCR rearrangement.…”