Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

AML1 (RUNX1) encodes a DNA-binding subunit of the CBF transcription factor family and is required for the establishment of definitive hematopoiesis. AML1 is one of the most frequently mutated genes associated with human acute leukemia, suggesting that genetic alterations of the gene contribute to leukemogenesis. Here, we report the analysis of mice carrying conditional AML1 knockout alleles that were inactivated using the Cre/loxP system. AML1 was deleted in adult mice by inducing Cre activity to replicate AML1 deletions found in human MDS, familial platelet disorder and rare de novo human AML. At a latency of 2 months after induction, the thymus was reduced in size and frequently populated by immature double negative thymocytes, indicating defective T-lymphocyte maturation, resulting in lymphatic diseases with 50% penetrance, including atypical hyperplasia and thymic lymphoma. Metastatic lymphomas to the liver and the meninges were observed. Mice also developed splenomegaly with an expansion of the myeloid compartment. Increased Howell-Jolly body counts indicated splenic hypofunction. Thrombocytopenia occurred due to immaturity of mini-megakaryocytes in the bone marrow. Together with mild lymphocytopenia in the peripheral blood and increased fractions of immature cells in the bone marrow, AML1 deficient mice display features of a myelodysplastic syndrome, suggesting a preleukemic state.
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PMID:AML1 deletion in adult mice causes splenomegaly and lymphomas. 1624 65

The characterization of leukemia-associated chromosome translocations has contributed relevant insights into our understanding of leukemia pathogenesis and has provided new specific tumor markers essential in prognostic assessment and minimal residual disease studies. The aim of this work is to study the frequency of AML1/ETO fusion gene in a series of Egyptian childhood AML cases. The clinical significance and prognostic implications of this aberration, including CR rate, duration of first CR, extramedullary leukemia (EML), and survival are investigated as well. Peripheral blood and/or bone marrow mononuclear cells were available for analysis from 78 children, all newly diagnosed with AML. AML1/ ETO fusion transcript was detected by the reverse transcriptase- polymerase chain reaction (RT-PCR) technique. Patients with de novo AML were treated by 2 courses of induction chemotherapy, followed by 4 courses of consolidation treatment if the patient achieved complete remission (CR). The marrow status was evaluated after each course in order to check bone marrow cellularity and presence of blasts. Patients with less than 5% blasts by the end of the second course of ADE passed to consolidation chemotherapy. Patients with more than 5% blasts by the end of the second course of ADE were excluded from the study. The AML1/ETO fusion transcript was detected by a singleround RT-PCR reaction and was found to be expressed in 15 out of 78 cases (19.2%). AML1/ETO positive patients were 7 girls and 8 boys, with ages ranging from 5 to 15 years. Seven cases (46.67%) belonged to FAB subtype M1, 7 (46.67%) M2, while only one case (6.67%) belonged to M5a subtype. Their total leukocytic counts ranged from 7.1 to 183.0 x 109/l with a median of 21.0 x 109/l. Their hemoglobin concentrations ranged from 4.8 to 10.3g/dl with a median of 7.4g/dl, while their platelet counts ranged from 6.0 to 96.0 x 109/l with a median of 25.5 x 109/l. Lymph nodes were enlarged in 8/15 cases (53.34%), hepatomegly was observed in 4/15 cases (26.67%), splenomegaly in 8/15 cases (53.34%), purpura in 6/15 cases (40%), while pallor was observed in all fifteen cases.Extramedullary leukemia occurred in 4/15 cases (26.67%). As regards the fate of the positive cases, thirteen cases (86.67%) attained complete remission (CR) following induction chemotherapy. Two patients (13.33%) died during induction in active disease. Eight patients were in complete continuous remission (CCR), four patients (26.67%) relapsed and died during relapse, and one patient (6.67%) died in complete remission due to severe neutropenia and infection. On comparing the AML1/ETO fusion gene status with overall survival, no significant difference was found between AML1/ETO positive and negative cases. Likewise, no difference could be found between positive and negative cases as regards disease-free survival (p=0.354). In conclusion, we report a frequency of 19.2% of AML1/ETO fusion gene in our newly diagnosed pediatric AML cases. Positive cases showed good response to induction therapy, as well as high complete remission rates, which are features of good prognosis. Key Words: Pediatric acute myeloid leukemia , AML1/ETO fusion gene , RT-PCR , Clinical outcome , Prognostic significance.
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PMID:AML1/ETO Fusion Gene in de novo Pediatric Acute Myeloid Leukemia: Clinical Significance and Prognostic Implications. 1883 34

Rare chronic myelogenous leukemia (CML) patients manifested as the primary blast phase without a chronic and accelerated phase. The occurrence of a t(8;21) translocation in secondary blast phase of CML or Philadelphia chromosome positive acute myelogenous leukemia (Ph+ AML) has been reported previously. No case of primary blast phase of chronic myelogenous leukemia (CML-BP) bearing one clone with t(9;22) and t(8;21) simultaneously has been reported. One Chinese patient presenting with extensive spontaneous ecchymosis and enlarged spleen diagnosed as acute myelogenous leukemia (AML) by smear and immunophenotype was given chemotherapy including daunorubicin 3 days and cytarabine 7 days without a tyrosine kinase inhibitor (TKI) drug at the beginning. Fresh frozen plasma and 4-factor prothrombin complex concentrate was also transfused for coagulation disorder. However, fusion genes BCR/ABL p210 and AML1/ETO were both positive and karyotype analysis showed the abnormalities of t(9;22) and t(8;21) in the same clones. Bone marrow aspirate on 7th day of chemotherapy indicated hypocellularity with 45% blasts remaining. Cytarabine was prolonged to nine days combined with imatinib 600 mg per day. His bone marrow aspirate after complete remission revealed t(8;21) clones disappearing, especially FISH of bone marrow smear detecting the BCR/ABL fusion signals in the basophilic erythroblasts, which confirmed his diagnosis as primary blast phase of CML rather than Ph+ AML. Thus, we report for the first time one patient diagnosed as primary blast phase of CML presenting with t(9;22) and t(8;21) simultaneously.
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PMID:Co-existence of t(9;22) and t(8;21) in primary blast phase of chronic myelogenous leukemia: clinical experience and literature review. 3193 3