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Detection of dual TEL-ABL transcripts and a Tel-Abl protein containing phosphotyrosine in a chronic myeloid leukemia patient

Leukemia volume 16, pages 294–297 (2002)Cite this article

Chronic myeloid leukemia (CML) is typically characterized by the presence of the Philadelphia chromosome (Ph), which encodes a fusion protein composed of 5′ BCR gene sequences fused to ABL gene sequences beginning at the second exon of the ABL gene.1 These Bcr-Abl proteins have several molecular forms, all of which have elevated tyrosine kinase activity.2 We have assayed more than 6000 blood/marrow samples from patients with CML by a Western blot procedure using anti-Abl monoclonal antibody termed 8E9, which readily detects all forms of the Bcr-Abl protein.3 In the last several years, another fusion involving the fusion of TEL sequences to ABL sequences was reported in cases of acute myeloid leukemia (AML)4 and acute lymphocytic leukemia (ALL).5 In addition, a TEL-ABL fusion was detected in a patient with a Ph-negative chronic myeloid leukemia.6 The TEL gene is a ubiquitously expressed gene that encodes an ETS-related transcription factor. It contains a predicted helix–loop–helix (HLH) motif at its N- terminus and an ETS DNA binding-domain at its C-terminus.7 The Tel-Abl protein is constitutively tyrosine phosphorylated and localizes to the cytoskeleton. These activities are dependent on the activated Abl tyrosine kinase and the highly conserved region of TEL termed the HLH domain involved in the oligomerization of the Tel-Abl fusion protein.

Here we report a Tel-Abl protein in blood cells from a patient with a chronic myeloid leukemia with a white blood count ranging from 18000 to 250000/μl. A 53-year-old male was referred to MDACC in May 1995 and was found to have a WBC of 22000/μl with 11% eosinophils, 0% blasts, 2% metamyelocytes, 58% polymorphonuclear and 1% band forms, 16% lymphocytes, 3% monocytes, hemoglobin of 13.1 g/dl and 378000/μl platelets. His bone marrow had 2.3% promyelocytes, 16.3% myelocytes, 26.8% metamyelocytes, 36.5% polymorphonuclear cells, 9.7% erythroid, 2% lymphoid cells and 0.5% monocytes. Cytogenetic analysis was diploid, but Western blot analysis revealed a 170 kDa Abl-related protein. Physical examination was normal without hepato- or splenomegaly; CT scan of the abdomen was normal as well. In October 1998, his WBC had increased to 160000/μl and his bone marrow was hypercellular with granulocytic hyperplasia. Cytogenetic analysis was again diploid. The patient was started on hydroxyurea, which he discontinued because of mouth ulcers and was then treated with IFNα at 3 MU/day. In February 1999 IFN therapy was discontinued because of a platelet count of 12000/μl. In September 1999, with essentially unchanged CBC, hepatomegaly was noted 10 cm below the costal margin (BCM), and in May 2000 increased to 15 cm BCM and a massive spleen of 16 cm BCM was palpated. WBC was 102000/μl with 2% myelocytes, 15% metamyelocytes, 51% polymorphonuclear cells, 5% lymphocytes, 4% monocytes, 5% eosinophils and 3% basophils, Hgb 12.5 g/dl and platelets 237000/μl, LDH 1019 IU/l. He was treated with hydrea 8 g/day and returned in July 2000 with WBC of 34000/μl, complaining of left upper quadrant (LUQ) pain. His spleen was 17 cm, and his liver 10 cm BCM. In August 2000 the patient presented to the emergency room, he was lethargic and his WBC had increased to 251000/μl. He underwent two aphereses and his WBC subsequently decreased to 18600/μl. He underwent splenectomy in September 2000 without complications. Histology showed a myeloproliferative disorder in the spleen and splenic hilar lymph node. A liver biopsy showed extramedullary hematopoiesis, predominantly erythroid and a benign bile duct proliferation within well-vascularized fibrous tissue consistent with mesenchymal hamartoma, with bile duct hamartomas (von Meyenberg complexes) in adjacent hepatic parenchyma. Six months later the patient's WBC was 32800/μl, Hgb 8.7 g/dl and platelets 415000/μl.

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  1. Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    H Lin, JQ Guo & RB Arlinghaus

  2. Departments of Leukemia and Blood and Marrow Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    M Andreeff

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Lin, H., Guo, J., Andreeff, M. et al. Detection of dual TEL-ABL transcripts and a Tel-Abl protein containing phosphotyrosine in a chronic myeloid leukemia patient. Leukemia 16, 294–297 (2002). https://doi.org/10.1038/sj.leu.2402353

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