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  • ionomycin NCS is a rare syndrome In case series of NCS

    2019-06-11

    NCS is a rare syndrome. In case series of NCS 14–47% were associated with of lymphoproliferative disorders [reviewed in [12]]. Survival is usually dictated by the underlying disease and short in the setting of aggressive malignancies. Since NCS may be a manifestation of an underlying malignancy it has to be taken seriously. Though imaging and CSF studies were negative in our patient the specimens collected were not high volume and we treated the patient with prophylactic IT methotrexate and cytarabine. Residual NCS is still present>2 years since initial presentation. We did not identify the actual etiology, but differential diagnosis includes impingement with lymphoma, BMN, previous exposure to chemotherapy with higher frequency among highly proliferating neoplasms [12].
    Conflict of interest
    Introduction T-cell prolymphocytic leukemia (T-PLL) is a rare type of peripheral T-cell leukemia with a naive T-cell phenotype [1]. The clinical features of T-PLL include marked hepatosplenomegaly and generalized lymphadenopathy with rapidly progressive lymphocytosis. The prognosis is generally poor due to resistance to chemotherapy, with a median survival ranging from 7.5 to 50 months [1–3]. Chromosomal abnormalities such as t(14;14)(q11;q32), inv(14)(q11;q32) and t(X;14)(q28;q11) have been identified in patients with T-PLL, which result in the rearrangement of the TCL1 or MTCP1 ionomycin with the T-cell receptor loci, which were thought to contribute to the pathogenesis of T-PLL [3]. We herein report a case of T-PLL with a novel ABL1 fusion gene which was fused to SEPT9, SEPT9-ABL1. The case exhibited strong resistance to the tyrosine kinase inhibitors (TKI) used against BCR-ABL1. This is the first report of T-PLL with an ABL1 fusion gene, and additionally, only the second report of a hematological malignancy with an ABL1 fusion gene that exhibited a poor response to TKI.
    Case report A 70-year-old male was admitted to our hospital due to leukocytosis. On a physical examination, lymphadenopathy extending from the bilateral cervical to supraclavicular regions with moderate hepatomegaly was noted. The laboratory data on admission were as follows: white blood cells (WBC), 248×109/L with 0% neutrophils, 1% lymphocytes, 1% monocytes, 0% eosinophils, 0% basophils and 98% atypical lymphocytes, which were medium-sized with pale cytoplasm and prominent nucleoli (Fig. 1A); red blood cells (RBC), 4110×109/L; hemoglobin (Hb), 12.4g/dl; and platelets (Plt), 171×109/L. Blood biochemistry was normal, except for elevated levels of lactate dehydrogenase and hepatobiliary enzymes. Bone marrow aspirate smears showed marked proliferation of atypical lymphocytes with a similar morphology to that of the peripheral blood cells. Using a cytogenetic analysis, six of six metaphases examined were 46, XY. A flow cytometric analysis showed that the atypical lymphocytes were positive for CD2, CD4, CD5 and CD7. A BCR-ABL FISH analysis showed no BCR-ABL signals, although 79 of 100 bone marrow cells exhibited atypical signals (ABL1: three copies and BCR: two copies in each cell) (Fig. 1B). The three ABL1 signals indicated either simple amplification of the ABL1 gene or the presence of ABL1 rearrangement. In order to examine these two possibilities, the 5′-terminal sequence of the ABL1 gene was analyzed using the 5′ RACE PCR method (SMARTer RACE cDNA Amplification Kit, Takara Bio, Shiga, Japan), according to the manufacturer׳s protocol. Sequencing of the PCR products demonstrated the fusion of exon 4 of SEPT9 to exon 2 of ABL1 (Fig. 1C), suggesting that the SEPT9-ABL1 fusion gene had the same breakpoint in ABL1 as that seen in BCR-ABL1. The presumed structure of the SEPT9-ABL1 fusion product is shown in Fig. 1D. A Western blot analysis revealed the expression and phosphorylation of SEPT9-ABL1, in addition to the phosphorylation of a downstream target CRKL, in the T-PLL cells obtained from the patient (Fig. 1E). Taking into account the patient׳s clinical, morphological, immunophenotypic and molecular features, he was diagnosed with T-PLL harboring SEPT9-ABL1. This is the first report of a novel SEPT9-ABL1 fusion gene in a patient with malignancy, as well as T-PLL harboring ABL1 fusion.