Activation of the interleukin-3 gene by chromosome translocation in acute lymphocytic leukemia with eosinophilia [see comments]

Abstract

The t(5;14)(q31;q32) translocation from B-lineage acute lymphocytic leukemia with eosinophilia has been cloned from two leukemia samples. In both cases, this translocation joined the IgH gene and the interleukin-3 (IL-3) gene. In one patient, excess IL-3 mRNA was produced by the leukemic cells. In the second patient, serum IL-3 levels were measured and shown to correlate with disease activity. There was no evidence of excess granulocyte/macrophage colony stimulating factor (GM-CSF) or IL-5 expression. Our data support the formulation that this subtype of leukemia may arise in part because of a chromosome translocation that activates the IL-3 gene, resulting in autocrine and paracrine growth effects.

Large T‐cell extradural lymphoma with concurrent marked cerebrospinal fluid eosinophilia in a dog

“…In humans, eosinophilic CSF secondary to lymphoma is infrequently reported with T‐cell lymphomas, 14‐23 and is a rare but treatable complication of Hodgkin lymphoma 24 . This phenomenon is considered to most likely be secondary to cytokine release by the neoplastic lymphocytes 23,25‐27 . Peripheral eosinophilia is used as a diagnostic or therapeutic marker in a variety of other neoplastic conditions 28,29 …”

“…24 This phenomenon is considered to most likely be secondary to cytokine release by the neoplastic lymphocytes. 23,[25][26][27] Peripheral eosinophilia is used as a diagnostic or therapeutic marker in a variety of other neoplastic conditions. 28,29 F I G U R E 3 (A) Cerebrospinal fluid from a 3-year-old male intact pit bull terrier that has a markedly increased nucleated cell count of 643 cells/uL (RI < 4 cells/ul), 90% of which are eosinophils.…”

B-ALL With t(5;14)(q31;q32); IGH-IL3 Rearrangement and Eosinophilia: A Comprehensive Analysis of a Peculiar IGH-Rearranged B-ALL

“…The relationship between IL3 and eosinophilia is also supported by the constant eosinophilia in all patients treated with recombinant IL3 for Blackfan-Diamond anemia in one study (6). The IL3-receptor has been hypothesized to be present on blast cells and to induce JAK-STAT-dependent cell survival and proliferation in an autocrine manner (4,7). The other part of the translocation involves the IGH gene, which is frequently rearranged via chromosomal translocations in mature B-cell neoplasms such as Burkitt leukemia/lymphoma, mantle cell or follicular lymphomas with MYC, CCND1, or BCL2 as partner genes, respectively, whose expression is upregulated (8).…”

“…The translocation t(5;14)(q31;q32) juxtaposes the IGH enhancer located on 14q32 to the IL3 gene on 5q31. The subsequent production of interleukin-3 (IL3) induces the maturation and release of eosinophils in the blood stream (3)(4)(5). The relationship between IL3 and eosinophilia is also supported by the constant eosinophilia in all patients treated with recombinant IL3 for Blackfan-Diamond anemia in one study (6).…”