images in haematology
Leukaemia cutis in atypical chronic myeloid leukaemia with a t(9;22) (p24;q11.2) leading to BCR-JAK2 fusion
BCR (exon 1)
A 44-year-old male presented with a violaceous papular scalp rash and bilateral small volume (1 cm) cervical lymphadenopathy. A full blood count showed a mild neutrophil leucocytosis (11.9 · 109/l) and left shift. The blood film was leucoerythroblastic with toxic changes and occasional tear drop poikilocytes. A skin biopsy demonstrated a dense dermal infiltrate comprising intermediate sized blast cells with granular cytoplasm. These cells stained positively with CD117, CD34 and CD43, consistent with granulocytic sarcoma [top left; haematoxylineosin stain (H&E)]. A bone marrow aspirate showed features of a myeloproliferative disorder, with granulocytic hyperplasia (1% myeloblasts), large hyperlobulated megakaryocytes and mild dyserythropoiesis. Trephine biopsy sections showed marked hypercellularity with effacement of normal marrow architecture; there was an increase of cells of neutrophilic and eosinophilic lineages, and megakaryocyte clustering with morphologically abnormal forms (top right; H&E). Karyotyping performed on the marrow aspirate revealed 46, XY, t(9;22)(p24;q11.2) in 23 of 50 cells examined (bottom left). Fluorescence in situ hybridization using the BCR/ABL1 dual fusion probe (Vysis) detected no fusion signals and molecular studies for BCR-ABL1 fusion transcripts [expected in association with t(9;22)(q34;q11)] were also negative. Further molecular studies were performed and an abnormal fusion transcript between exon 1 of BCR and exon 17 of JAK2 was amplified and
JAK2 (exon 17)
sequenced from the patient’s bone marrow (bottom right). The BCR exon 1 is in-frame with the tyrosine kinase domain of JAK2. This unique BCR-JAK2 fusion gene was clinically manifest as an MPD with early extramedullary transformation. A previous report of an MPD with a BCR-JAK2 fusion (Griesinger et al, 2005) with different breakpoints also showed relatively early blast crisis. Whether BCR-JAK2 positive MPD represents a distinct clinical-pathological entity requires further study. Steven W. Lane1 David J. Fairbairn1 Catherine McCarthy1 Adayapalam Nandini1 Joanna Perry-Keene2 Glen A. Kennedy1 1
Departments of Haematology, and 2Anatomical Pathology, Royal
Brisbane and Women’s Hospital, Brisbane, Australia. E-mail:
[email protected]
Reference Griesinger, F., Hennig, H., Hillmer, F., Podleschny, M., Steffens, R., Pies, A., Wormann, B., Haase, D. & Bohlander, S.K. (2005) A BCR– JAK2 fusion gene as the result of a t(9;22)(p24;q11.2) translocation in a patient with a clinically typical chronic myeloid leukemia. Genes Chromosomes and Cancer, 44, 329–333.
ª 2008 The Authors Journal Compilation ª 2008 Blackwell Publishing Ltd, British Journal of Haematology, 142, 503
First published online 5 June 2008 doi:10.1111/j.1365-2141.2008.07164.x
