Acute myeloid leukemia presenting with leukopenia: a distinct entity
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE20482 | GEO | 2010/03/01
SECONDARY ACCESSION(S): PRJNA125171
REPOSITORIES: GEO
Similar Datasets
Project description:Core binding factor (CBF) leukemias, characterized by either inv(16)/t(16;16) or t(8;21), constitute acute myeloid leukemia (AML) subgroups with favorable prognosis. However, there exists substantial biological and clinical heterogeneity within these cytogenetic groups, which is not fully reflected by the current classification system. To improve the molecular characterization we profiled gene expression in a large series (n=93) of AML patients with CBF leukemia [inv(16) n=55, t(8;21) n=38]. By unsupervised hierarchical clustering we were able to define a subgroup of CBF cases (n=35) characterized by shorter overall survival times (P=0.03). While there was no obvious correlation with fusion gene transcript levels, FLT3 tyrosine kinase domain, KIT, and NRAS mutations, the newly defined inv(16)/t(8;21)-subgroup was associated with elevated white blood cell counts and FLT3 internal tandem duplications (P=0.011 and P=0.026, respectively). Supervised analyses of gene expression suggested alternative cooperating pathways leading to transformation. In the ?favorable? CBF leukemias anti-apoptotic mechanisms and deregulated mTOR-signaling, and in the newly defined ?unfavorable? subgroup aberrant MAPKinase-signaling and chemotherapy-resistance mechanisms might play a role. While the leukemogenic relevance of these signatures remains to be validated, their existence nevertheless supports a prognostically relevant biological basis for the heterogeneity observed in CBF leukemia. A reference experiement design type is where all samples are compared to a common reference. Using regression correlation
2007-08-09 | E-GEOD-8653 | biostudies-arrayexpress
Project description: Not available
| S-EPMC7175754 | biostudies-literature
Project description:Core binding factor (CBF) leukemias, characterized by either inv(16)/t(16;16) or t(8;21), constitute acute myeloid leukemia (AML) subgroups with favorable prognosis. However, there exists substantial biological and clinical heterogeneity within these cytogenetic groups, which is not fully reflected by the current classification system. To improve the molecular characterization we profiled gene expression in a large series (n=93) of AML patients with CBF leukemia [inv(16) n=55, t(8;21) n=38]. By unsupervised hierarchical clustering we were able to define a subgroup of CBF cases (n=35) characterized by shorter overall survival times (P=0.03). While there was no obvious correlation with fusion gene transcript levels, FLT3 tyrosine kinase domain, KIT, and NRAS mutations, the newly defined inv(16)/t(8;21)-subgroup was associated with elevated white blood cell counts and FLT3 internal tandem duplications (P=0.011 and P=0.026, respectively). Supervised analyses of gene expression suggested alternative cooperating pathways leading to transformation. In the ?favorable? CBF leukemias anti-apoptotic mechanisms and deregulated mTOR-signaling, and in the newly defined ?unfavorable? subgroup aberrant MAPKinase-signaling and chemotherapy-resistance mechanisms might play a role. While the leukemogenic relevance of these signatures remains to be validated, their existence nevertheless supports a prognostically relevant biological basis for the heterogeneity observed in CBF leukemia. A reference experiement design type is where all samples are compared to a common reference. Keywords: reference_design
2007-08-09 | GSE8653 | GEO
Project description: Not available
| S-EPMC4925399 | biostudies-literature
Project description:Acute myeloid leukemia (AML) is a devastating disease with an incidence that progressively increases with advancing age. Currently, only ∼40% of younger and 10% of older adults are long-term survivors. If untreated, the overall prognosis of AML remains dismal. Initiation of therapy at diagnosis is usually urgent. Barriers to successful therapy for AML are the attendant toxicities directly related to chemotherapy or those associated with inevitable aplasia. Organ dysfunction often further complicates such toxicities and may even be prohibitive. There are few guidelines to manage such patients and the fear of crossing the medico-legal abyss may dominate. Such clinical scenarios provide particular challenges and require experience for optimal management. Herein, we discuss select examples of common pretreatment comorbidities, including cardiomyopathy, ischemic heart disease; chronic renal failure, with and without dialysis; hepatitis and cirrhosis; chronic pulmonary insufficiency; and cerebral vascular disease. These comorbidities usually render patients ineligible for clinical trials and enormous uncertainty regarding management reigns, often to the point of withholding definitive therapy. The scenarios described herein emphasize that with appropriate subspecialty support, many AML patients with comorbidities can undergo therapy with curative intent and achieve successful long-term outcome.
| S-EPMC5524532 | biostudies-other
Project description:The effect of prior malignancy on the risk of developing, and prognosis of, acute lymphoblastic leukemia (ALL) is unknown. This observational study utilized the California Cancer Registry to estimate the risk of developing ALL after a prior malignancy using standardized incidence ratios (SIRs, 95% confidence intervals). ALL occurring after a malignancy with an SIR>1 (increased-risk (IR) malignancies) was considered secondary ALL (s-ALL). Adjusted hazard ratios (aHRs, 95% confidence intervals) compared the effect of s-ALL with de novo ALL on overall survival. A total of 14?481 patients with ALL were identified (1988-2012) and 382 (3%) had a known prior malignancy. Any prior malignancy predisposed patients to developing ALL: SIR 1.62 (1.45-1.79). Hematologic malignancies (SIR 5.57, 4.38-6.98) and IR-solid tumors (SIR 2.11, 1.73-2.54) increased the risk of developing ALL. s-ALL increased the risk of death compared with de novo ALL (aHR 1.38 (1.16-1.63)) and this effect was more pronounced among younger patients (age<40 years: aHR 4.80 (3.15-7.30); age?40 years: aHR 1.40 (1.16-1.69)) (interaction P<0.001). This population-based study demonstrates that s-ALL is a distinct entity that occurs after specific malignancies and carries a poor prognosis compared with de novo ALL, particularly among patients <40 years of age.
| S-EPMC5709750 | biostudies-literature
Project description:We report a case of t(8;21) acute myeloid leukemia presenting as severe aplastic anemia. While initial bone marrow biopsy lacked any cytogenetic abnormalities in 20 analyzed metaphases, repeat bone marrow biopsy eight days later demonstrated this translocation. Initial cytogenetic analysis of 20 metaphases was therefore insufficient to make the diagnosis of hypocellular acute myeloid leukemia. We discuss that further complementary molecular tests, such as CGH, would likely provide a more robust diagnosis of hematopoietic diseases.
| S-EPMC4081983 | biostudies-literature
Project description:Myeloid/lymphoid neoplasm with eosinophilia (MLN-Eo) is a World Health Organization (WHO) established category of hematologic malignancies primarily arising in adults. We discuss an 8-month-old infant who presented with clinical features similar to those of juvenile myelomonocytic leukemia (JMML) but who was diagnosed with MLN-Eo driven by an ETV6-FLT3 fusion. Results of patient-derived leukemia ex vivo studies demonstrated increased sensitivity to type I FLT3 inhibitors as compared with type II inhibitors. Treatment with the type I inhibitor gilteritinib resulted in complete immunophenotypic and cytogenetic remission. This patient subsequently underwent a hematopoietic stem cell transplant and remains in complete remission 1 year later. This is the youngest patient reported with an ETV6-FLT3 fusion and adds to the mounting reports of FLT3-rearranged MLN-Eo, supporting its addition to the WHO classification. Furthermore, this case highlights the clinical utility of ex vivo drug testing of targeted therapies.
| S-EPMC8045514 | biostudies-literature
Project description:Label-free quantitation dataset from 44 representative Acute Myeloid Leukemia (AML) patients from the LAML TCGA dataset, and 6 healthy bone marrow derived controls including 3 lineage-depleted and 3 CD34+ selected bone marrows.
2022-03-09 | MSV000089029 | MassIVE
Project description:A deep-scale proteome and phosphoproteome database from 44 representative Acute Myeloid Leukemia (AML) patients from the LAML TCGA dataset, and 6 healthy bone marrow derived controls including 3 lineage-depleted and 3 CD34+ selected bone marrows.
2022-03-07 | MSV000089012 | MassIVE