Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The novel fusion protein DT(388)IL3, composed of the catalytic and translocation domains of diphtheria toxin (DT(388)) fused with a Met-His linker to human interleukin 3 (IL-3), was tested for anti-leukemia efficacy in an in vivo model of differentiated human acute myeloid leukemia (AML). Six-week-old female SCID mice were irradiated with 350 cGy, inoculated 24 h later with 20 million (i.v., i.p., or s.c.) TF1 cells transfected with the v-SRC oncogene, and treated i.p., starting 24 h later, with up to five daily injections of saline, DT(388)IL3 (2 microg), DT(388)GMCSF (2 microg), DAB(389)IL2 (2 microg), or cytarabine (80 microg) or two weekly injections of anti-CD33-calicheamicin conjugate (5 microg). Animals were monitored twice daily, and moribund animals killed and necropsied. Control animals had a median disease-free survival (DFS) of 37 days (i.v., n = 45), 35 days (i.p., n = 20), and 21 days (s.c., n = 20), respectively. Only 5/49 (10%) of the DT(388)IL3 treated i.v. inoculated animals died with leukemia. Median DFS with i.v., i.p. and s.c. tumor inoculated animals was prolonged by fusion protein treatment to >120 days, 66 days and 31 days (P < 0.001, = 0.0003, and = 0.0006), respectively. Median DFS with s.c. tumor inoculated animals was also prolonged by other active anti-leukemia agents (DT(388)GMCSF, cytarabine and anti-CD33-calicheamicin) relative to controls by 67%, 172% and 47% (P < 0.0001, <0.0001, and =0.0004), respectively. In contrast, median DFS with s.c. tumor inoculated animals treated with DAB(389)IL2 non-significantly reduced by 13% relative to controls (P = 0.21). Thus, DT(388)IL3 fusion protein demonstrates in vivo anti-leukemia efficacy and warrants further preclinical development for treatment of chemo-resistant, IL-3 receptor positive AML patients.
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PMID:Diphtheria toxin-interleukin-3 fusion protein (DT(388)IL3) prolongs disease-free survival of leukemic immunocompromised mice. 1252 73

In this case report, we present a pediatric case of lymphomatoid granulomatosis (LG) with onset just after the completion of chemotherapy for childhood acute myeloid leukemia (AML). After the completion of maintenance therapy, the patient was admitted to our clinic with a complaint of cough. Radiologic examinations revealed nodular lesions in lungs, liver, and kidney. His bone marrow was in remission. The histopathologic examination of the open lung biopsy was consistent with LG. He received only one cycle of cyclophosphamide and high-dose methyl prednisolone treatment and continued to receive interferon (IFN) alpha-2b therapy for 18 months. This treatment regimen resulted in an excellent response. In conclusion, LG may occur after the treatment of pediatric AML as a rare complication and IFN alpha-2b may be an effective treatment choice in these patients.
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PMID:A pediatric case of lymphomatoid granulomatosis with onset after completion of chemotherapy for acute myeloid leukemia. 1257 71

The incidence of systemic fungal infections increased during the last two decades. Rare fungi, such as Mucor, Fusarium and Paecilomyces, are emerging as causes of systemic fungal infections in immunocompromised hosts. There are reports of cutaneous infections, endophthalmitis, keratitis, sinusitis, neuropathy and fungemia in immunocompromised and immunocompetent adult patients. We report a 5 years old neutropenic patient with acute myeloid leukemia treated with multiple courses of chemotherapy, with a fungemia caused by Paecilomyces lilacinus (PL). His initial clinical course was characterized by fever, skin lesions, respiratory distress and shock. Blood and bone marrow cultures were positive. The patient was treated with amphotericin B and itraconazole with a good clinical response.
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PMID:[Paecilomyces lilacinus systemic infection in an immunocompromised child]. 1264 23

A 75-year-old man was admitted because of right knee joint pain in December 1999. He had suffered from acute myelocytic leukemia (AML: M0) in November 1994 and achieved the first complete remission (CR) then. His AML relapsed in August 1996, but fortunately he achieved a second CR. Radiographical bone examination revealed osteolytic lesions in his right knee and bone scintigraphy showed uptake in the right knee and the middle part of the left femur. MRI also revealed a low attenuation signal in the left femur. He had no abnormal findings in peripheral blood or bone marrow. Histological examination of the biopsied bone tissue showed a diffuse proliferation of round cells with medium-sized or large nuclei. These cells were histochemistrically negative for myeloperoxidase and naphtol-ASD-chloroacetate esterase, and were also negative for lysozyme, cytokeratin 7, 9, 20, EMA, CEA, CD3, CD79a on immunohistochemistry, but were positive for CD43, CD56. In immunophenotypic analysis of these cells by flow cytometry, CD7, CD13, CD33, CD41, CD56 were revealed to be strongly positive. On the basis of these findings we diagnosed these tumors as granulocytic sarcomas (GS), extramedullary recurrence of AML M7. Although radiation (36Gy) to these tumors brought a temporary relief of the pain, he died of systemic relapse of AML in February 2001. When presented CD7+ AML M0 had been diagnosed, but GS cells were also positive for CD 56 and CD41. Although CD56 had not been examined initially, he might have been had myeloid/NK cell precursor acute leukemia and CD41 might be acquired later in the course of the disease. It is known that AML M0, M7 and myeloid/NK cell precursor acute leukemia have poor prognoses, nevertheless he survived for 6 years. It may be that intensive and repeated chemotherapy for AML can obtain excellent outcome in the elderly cases in good systemic condition and with favourable prognostic factors.
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PMID:[Acute myelocytic leukemia (M0) in an elderly patient with relapsed granulocytic sarcoma (M7) of bone during the second period of complete remission 5 years after onset]. 1270 54

Castleman disease (CD) is a rare heterogeneous lymphoproliferative disease characterized by clinical symptoms due to an excess of interleukin-6 (IL-6) or IL-6-like activity. We describe the first case of CD associated with acute myelogenous leukemia (AML). A 55-year-old man presented with skin rash on his face and multiple cervical lymphadenopathy. The results of examination of his lymph node biopsy specimen led to a diagnosis of CD. The symptoms resolved after the administration of prednisolone. Three years after the onset of CD, the patient's white blood cell count had increased to 63.4 x 10(9)/L. His bone marrow aspirate showed that approximately 80% of cells were leukemic, including well-differentiated monocytic cells A diagnosis of AML M5b was made. The patient died of invasive pulmonary aspergillosis after chemotherapy.
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PMID:Acute myelogenous leukemia M5b developed during clinical remission of Castleman disease. 1273 71

CD64, the high affinity receptor for IgG (FcgammaRI) is expressed on acute myeloid leukemia blast cells and has recently been described as a specific target for immunotherapy. To generate a recombinant immunotoxin, the anti-CD64 single chain fragment (scFv) m22 was cloned into the bacterial expression vector pBM1.1 and fused to a deletion mutant of Pseudomonas exotoxin A (ETA'). Genetically modified Escherichia coli BL21 Star (DE3) were grown under osmotic stress conditions in the presence of compatible solutes. After isopropyl beta-D-thiogalactoside induction, the 70-kDa His(10)-tagged m22(scFv)-ETA' was directed into the periplasmic space and purified by a combination of metal-ion affinity and molecular size-chromatography. The characteristics of the recombinant protein were assessed by ELISA, flow cytometry, and toxicity assays, using CD64-positive AML cells. Binding specificity of m22(scFv)-ETA' was verified by competition with the parental anti-CD64 monoclonal antibody m22. The recombinant immunotoxin showed significant toxicity toward the CD64-positive cell lines HL-60 and U937 reaching 50% inhibition of cell proliferation at a concentration (IC(50)) of 11.6 ng/ml against HL-60 cells and 12.9 ng/ml against U937 cells. Approximately 41% of primary leukemia cells from a patient with CD64-positive AML were driven into early apoptosis by m22(scFv)-ETA' as measured by flow cytometric analysis. This is the first article documenting the specific cytotoxicity of a novel recombinant immunotoxin with major implications for immunotherapy of CD64-positive diseases.
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PMID:Recombinant CD64-specific single chain immunotoxin exhibits specific cytotoxicity against acute myeloid leukemia cells. 1467 4

We describe a patient with acute myelogenous leukemia (AML) who was complicated with severe tumor lysis syndrome (TLS) after a single day of chemotherapy; a previously unreported occurrence. A 48-year-old man was admitted because of fever and bleeding tendency, and was diagnosed as having AML: M1. His white blood cell count (WBC) was 66, 300/microliter with 96% myeloblasts. Chemotherapy with idarubicin and cytarabine was started. On the second day of the therapy, he developed acute renal failure (ARF) and deterioration of disseminated intravascular coagulation (DIC) with a marked reduction in his WBC (8500/microliter). Immediately after a diagnosis of tumor lysis syndrome (TLS), the following chemotherapy was discontinued. Hemodiafiltration and hemofiltration were initiated to treat the ARF, concomitant with anticoagulant and antifibrinolysis therapy for the DIC. Chemotherapy with daunorubicin and cytarabine was resumed on the 12th day, recognizing a regrowth of leukemic cells. Thereafter a complete remission was achieved without recurrence of the TLS.
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PMID:[Acute myelogenous leukemia complicated with severe tumor lysis syndrome after a single day of idarubicin/cytarabine chemotherapy]. 1468 78

A 31-year-old man who underwent chemotherapy and bone marrow transplantation to treat acute myeloblastic leukemia was admitted to our department complaining of high fever and hypotension. His physical examination revealed warm shock state, eruptions resembling that seen in systemic lupus erythematosus on his face and cyanosis in his fingers. We diagnosed septic shock and idiopathic skin eruption on his face. Following treatment with blood transfusion, anticoagulant, antibiotics, respirator and continuous arteriovenous hemofiltration and dialysis, the patient's condition gradually improved. The eruptions on his face first observed at admission progressed with a worsening of his disseminated intravascular coagulation (DIC), and subsided with an improvement in his DIC. A biopsy of the eruption was taken and pathological findings of the eruption revealed multiple micro-fibrin depositions of the dermis. The skin necrosis in purpura fulminans often begins in the distal extremities. But our patient developed this uncommon skin eruption on his face. Patients with an idiopathic skin eruption resembling a butterfly rash in a septic patient should be considered to complicate DIC as in the present case.
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PMID:An idiopathic skin eruption resembling a butterfly rash in a septic patient with disseminated intravascular coagulation following bone marrow transplantation. 1506 Apr 23

Haploinsufficiency of the NSD1 gene is a hallmark of Sotos syndrome, and rearrangements of this gene by translocation can cause acute myeloid leukemia. The NSD1 gene product is a SET-domain histone lysine methyltransferase that has previously been shown to interact with nuclear receptors. We describe here a novel NSD1-interacting protein, Nizp1, that contains a SCAN box, a KRAB-A domain, and four consensus C2H2-type zinc fingers preceded by a unique finger derivative, referred to herein as the C2HR motif. The C2HR motif functions to mediate protein-protein interaction with the cysteine-rich (C5HCH) domain of NSD1 in a Zn(II)-dependent fashion, and when tethered to RNA polymerase II promoters, represses transcription in an NSD1-dependent manner. Mutations of the cysteine or histidine residues in the C2HR motif abolish the interaction of Nizp1 with NSD1 and compromise the ability of Nizp1 to repress transcription. Interestingly, converting the C2HR motif into a canonical C2H2 zinc finger has a similar effect. Thus, Nizp1 contains a novel type of zinc finger motif that functions as a docking site for NSD1 and is more than just a degenerate evolutionary remnant of a C2H2 motif.
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PMID:Nizp1, a novel multitype zinc finger protein that interacts with the NSD1 histone lysine methyltransferase through a unique C2HR motif. 1516 84

Two acute leukemia cases who presented autoimmune thyroid diseases after bone marrow transplantation (BMT) are described with reference to the pathogenesis of their autoimmune clones. A 37-year old Japanese woman developed Graves' hyperthyroidism 39 months after allogeneic BMT for acute myeloid leukemia (AML) donated from her sister. Although both donor and recipient were euthyroid and negative for thyroid autoimmunity before BMT, the donor was positive for anti-nuclear and anti-single strand DNA autoantibodies. Studies on polymorphism for variable number of tandem repeat region of T-cell receptor gene suggested that the lymphocytes responsible for the hyperthyroidism were of donor origin. The second case was a 12-year-old Japanese schoolboy who presented nongoitrous hypothyroidism 2 years after autologous BMT for acute lymphoblastic leukemia (ALL). He had been clinically euthyroid before transplantation. Family history revealed that his mother and sister had a history of Graves' disease. His serum was positive for thyroid-stimulation blocking antibody. It is highly likely that the autoimmune process was activated after transient immune suppression during peri-BMT period in this patient. Pathogenesis, incidence, and observed time lag between BMT and development of autoimmune thyroid diseases were discussed.
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PMID:Appearance of thyroid stimulating and blocking immunoglobulins after bone marrow transplantation: presentation of two contrasting cases. 1535 1


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