Therapy-related AML

Godley, Lucy A.; Beau, Michelle M. Le

doi:10.1007/978-1-59745-322-6_4

Cited by 2 publications

(1 citation statement)

References 112 publications

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“…Features that are fairly common in de novo acute leukemia, such as hepatomegaly, splenomegaly, lymphadenopathy, gingival hyperplasia, skin rash, or neurological complications, are notably absent from the presentations of patients with t-MDS/t-AML. Bone marrow biopsies typically reveal hypercellularity with some degree of marrow fibrosis, although hypocellular and even aplastic marrows can be seen (Godley & Le Beau, 2007).…”

Section: Clinical Featuresmentioning

confidence: 99%

Therapy-Related Acute Myeloid Leukemias

Guenova¹,

Balatzenko²,

Mihaylov³

2013

Leukemia

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Section: Clinical Featuresmentioning

confidence: 99%

Therapy-Related Acute Myeloid Leukemias

Guenova¹,

Balatzenko²,

Mihaylov³

2013

Leukemia

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Knockdown of Hnrnpa0, a del(5q) gene, alters myeloid cell fate in murine cells through regulation of AU-rich transcripts

et al. 2014

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© F e r r a t a S t o r t i F o u n d a t i o nhave a profound impact upon hematopoiesis, and consequently contribute to the changes seen in t-MN patients.In this study, we now add HNRNPA0 to the growing list of AUBPs that are recognized for their vital roles in hematopoiesis and leukemogenesis. Herein, we show that HNRNPA0 is highly expressed in hematopoietic stem cells, and its expression exhibits dynamic changes during the course of differentiation. Deletion of a single allele of HNRNPA0 is associated with haploinsufficient transcript levels in CD34 + cells from t-MN patients with a del(5q). Modeling HNRNPA0 haploinsufficiency in mouse cells alters myeloid lineage fate, in part through changes in the expression of ARE-containing genes, suggesting that a decreased dose of HNRNPA0 in t-MN patients may contribute to leukemogenesis. Moreover, we determined that ARE mRNAs in t-MN patients with a del(5q) are enriched in transcripts that encode proteins associated with increased growth and proliferation. Methods Retroviral transduction and in vitro differentiation of PUER and primary mouse hematopoietic cellsA short interfering RNA hairpin (shRNA), designed to match bases 288 to 306 of the open reading frame of Hnrnpa0 with a 9 nucleotide loop in the center, or a scrambled, irrelevant sequence, 17 was cloned into pBanshee-GFP (an MSCV-based construct with P CMV -driven GFP). The PUER cell line or mouse bone marrow cells from BALB/cAnNTac mice (Taconic, Hudson, NY, USA) were transduced by spinoculation with viral supernatants from HEK-293T cells co-transfected with the shRNA-containing pBanshee and pCL-ECO packaging plasmids (Imgenex, San Diego, CA, USA) using Effectene (Qiagen, Germantown, MD, USA). Two days post infection, the cells were sorted on a FACSAria (BD Biosciences, San Jose, CA, USA) for GFP positivity. All animal studies were approved by the University of Chicago Institutional Animal Care and Use Committee and mice were housed in a fully-AALAC-accredited facility. GFP + sorted PUER cells, expressing the Hnrnpa0 or control shRNA, were expanded in IL-3 for four days and then treated with 1-5 nM 4-hydroxytamoxifen (4-OHT, >98% (TLC) Z-isomer, Sigma, St. Louis, MO, USA) to induce macrophage differentiation. For gene expression, flow cytometry and morphological analyses, cells were sampled at 24 h, 4 days, and 7days, respectively. GFP + bone marrow cells were plated in MethoCult GF M3434 (StemCell Technologies, Vancouver, BC, Canada). After 12 days of incubation, colonies of greater than 50 cells were scored for morphology by inverted light microscopy. Cells were then collected and stained with Mac-1 (CD11b) antibodies in combination with either F4/80 or Gr-1 (Ly-6G) antibodies, and analyzed on a FASCanto benchtop flow cytometric analyzer (BD Biosciences, San Jose, CA, USA). Patient samplesAll 38 t-MNs used for gene expression profiling analysis were obtained from patients treated with chemotherapy and/or radiation therapy at the University of Chicago who were diagnosed with t-MN between January 1984...

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Therapy-related AML

Cited by 2 publications

References 112 publications

Therapy-Related Acute Myeloid Leukemias

Therapy-Related Acute Myeloid Leukemias

Knockdown of Hnrnpa0, a del(5q) gene, alters myeloid cell fate in murine cells through regulation of AU-rich transcripts

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