Abstract
BackgroundB-cell acute lymphoblastic leukemia (B-ALL) is the most common malignancy in pediatric patients and the leading cause of cancer-related death in children and young adults. Translocations of 9p24 involving JAK2 (9p24) and gain-of-function mutations of JAK2 with subsequent activation of the JAK2 kinase have been described in several hematological malignancies including B-ALL. However, rearrangements involving JAK2 are rare in B-ALL as only few cases have been described in the literature.FindingsHerein, we present a case of pediatric B-ALL whose conventional cytogenetics revealed an abnormal karyotype with a reciprocal translocation involving 9p24 (JAK2) and 12p11.2. Fluorescence in situ hybridization (FISH) studies using the RP11-927H16 Spectrum Green JAK2 probe on previously G-banded metaphases confirmed the involvement of JAK2 in this rearrangement. Further FISH studies on the same previously G-banded metaphases using the LSI MLL probe helped to characterize an insertion of MLL into 6q27 as an additional abnormality in this karyotype. FISH studies performed on interphase nuclei also revealed an abnormal clone with MLL rearrangements in 23.6% of the nuclei examined as well as an abnormal clonal population with a deletion of the 5'IGH@ region in 88.3% of the nuclei examined.ConclusionsRearrangements of 9p24 can result in constitutive activation of JAK2, and have been observed in B-ALL. Rearrangements of the MLL gene have also been described extensively in B-ALL. However, rearrangements of MLL with a partner at 6q27 and in conjunction with a translocation involving JAK2 have not been previously described. This case pinpoints the importance of FISH and conventional cytogenetics to characterize complex rearrangements in which JAK2 and MLL are involved. The therapeutic targeting of JAK2 and MLL in cases like this may be prognostically beneficial.
Highlights
Abnormalities involving JAK2 (9p24) have been seen in B-cell acute lymphoblastic leukemia (B-ALL), but most often via point mutations involving the pseudokinase domain, R683 [1,2]
Rearrangements of 9p24 can result in constitutive activation of JAK2, and have been observed in B-ALL
Rearrangements of MLL with a partner at 6q27 and in conjunction with a translocation involving JAK2 have not been previously described. This case pinpoints the importance of Fluorescence in situ hybridization (FISH) and conventional cytogenetics to characterize complex rearrangements in which JAK2 and MLL are involved
Summary
Abnormalities involving JAK2 (9p24) have been seen in B-ALL, but most often via point mutations involving the pseudokinase domain, R683 [1,2]. Activation of JAK2 occurs via gene fusions encoding chimeric proteins in which the kinase domain of JAK2 is fused to another cellular gene that provides a dimerization or oligomerization interface to the JAK2 kinase domain, leading to constitutive activation [1,2,3,4,5]. This case pinpoints the fact that JAK2 rearrangements may play an important role in the pathogenesis of lymphoblastic leukemias. Rearrangements involving JAK2 are rare in B-ALL as only few cases have been described in the literature
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