This hypothesis is supported by data suggesting that mutations in the human NF1 gene are causally associated with the development of juvenile chronic myelogenous leukemia (K. M. Shannon, P. O'Connell, G. A. Martin, D. Paderanga, K. Olson, P. Dinndorf, and F. McCormick, N. Engl.J. Med.
JCML is characterized by a spontaneous growth of granulocyte-macrophage progenitors that show a striking hypersensitivity to granulocyte-macrophage colony-stimulating factor.
These data show that TEL, previously shown to be fused to the platelet-derived growth factor receptor beta in chronic myelomonocytic leukemia, can be implicated in the pathogenesis of leukemia through its fusion to either a receptor tyrosine kinase or a transcription factor.
These data show that TEL, previously shown to be fused to the platelet-derived growth factor receptor beta in chronic myelomonocytic leukemia, can be implicated in the pathogenesis of leukemia through its fusion to either a receptor tyrosine kinase or a transcription factor.
We studied 71 children, including 28 with bone marrow monosomy 7 syndrome (Mo7), 35with juvenile chronic myelogenous leukemia (JCML), three with other forms of preleukemia, and five with acute myelogenous leukemia (AML), for activating mutations of KRAS and NRAS.
We studied 71 children, including 28 with bone marrow monosomy 7 syndrome (Mo7), 35with juvenile chronic myelogenous leukemia (JCML), three with other forms of preleukemia, and five with acute myelogenous leukemia (AML), for activating mutations of KRAS and NRAS.
These data suggest that N-ras gene mutations may be involved in the pathogenesis and/or prognosis of JCML and provide further evidence that JCML is an entity distinct from CML.
Despite the presence of a measurable amount of GM-CSF in JCML cell culture supernatants, GM-CSF-specific mRNA in CFU-C cells of four cases was not detected by RT-PCR.
These data further support a central role for IL-1 beta in the pathogenesis of JCML and suggest that the use of IL-1 Ra could represent a novel therapeutic strategy against this disorder.
These data further support a central role for IL-1 beta in the pathogenesis of JCML and suggest that the use of IL-1 Ra could represent a novel therapeutic strategy against this disorder.
These data further support a central role for IL-1 beta in the pathogenesis of JCML and suggest that the use of IL-1 Ra could represent a novel therapeutic strategy against this disorder.
We therefore analyzed samples obtained from 57 patients with a variety of hematologic malignancies (21, acute myelogenous leukemia; 14, acute lymphoblastic leukemia; 12, Philadelphia chromosome-positive chronic myelogenous leukemia [blast phase] or acute leukemia; 5, chronic lymphocytic leukemia; and 5, chronic myelomonocytic leukemia) for expression of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) transcripts on Northern blots.
We therefore analyzed samples obtained from 57 patients with a variety of hematologic malignancies (21, acute myelogenous leukemia; 14, acute lymphoblastic leukemia; 12, Philadelphia chromosome-positive chronic myelogenous leukemia [blast phase] or acute leukemia; 5, chronic lymphocytic leukemia; and 5, chronic myelomonocytic leukemia) for expression of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) transcripts on Northern blots.
Chromosomal deletions of band 13q14 occur recurrently in BCR/ABL negative chronic myeloproliferative disorders (CMPD), including myelosclerosis with myeloid metaplasia (MMM), polycythemia vera (PV), essential thrombocythemia (ET), juvenile chronic myeloid leukemia (JCML), and the so-called BCR/ABL- chronic myeloid leukemia (CML).
We report a case of chronic myelomonocytic leukemia in which cytogenetic analysis revealed a 47,XY, +1, +der(7)del(7)(q32q36)ins(7;1)(q32;p36.3p22) chromosomal constitution.
The TEL/platelet-derived growth factor beta receptor (PDGF beta R) fusion in chronic myelomonocytic leukemia is a transforming protein that self-associates and activates PDGF beta R kinase-dependent signaling pathways.
The transient thrombocythemia may relate to a regulator of megakaryocytopoiesis located in the vicinity of the NF1 gene or to the excessive risk of chronic myelomonocytic leukemia in neurofibromatosis.
Depending on the classification system used, they comprised two cases of chronic myelomonocytic leukemia (CMMoL) of which one can be reclassified as juvenile chronic myeloid leukemia (JCML) and one cases of refractory anemia with excess of blasts (RAEB) or an alternative diagnosis of atypical CML.
A patient with a 17-month history of myelodysplastic syndrome (refractory anemia with excess blasts that evolved into chronic myelomonocytic leukemia), which was treated with transfusions and erythropoietin, developed abdominal and inguinal lymphadenopathy.
Our findings identify the molecular basis for the autocrine TNFalpha activation of the GM-CSF gene in JMML and suggest potential novel and specific approaches for the treatment of this aggressive childhood leukemia.
These results indicate that the aberrant, constitutive GM-CSF gene activation in JMML is maintained by TNFalpha-mediated activation of NF-kappaB/Rel proteins.