Hox regulation of normal and leukemic hematopoietic stem cells

Abramovich, Carolina; Humphries, R. Keith

doi:10.1097/01.moh.0000160737.52349.aa

Cited by 141 publications

(97 citation statements)

References 97 publications

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“…MiR-10a regulates translation of HOX genes 14 that have important roles in regulation of early stages of hematopoiesis, including self-renewal of HSCs. 37 Thus, reduction of miR-10a level in advanced MDS may induce (through upregulation of HOX genes) conversion of BM HSCs to leukemic cells, and its decrease might be a marker of MDS progression.…”

Section: Discussionmentioning

confidence: 99%

Distinctive microRNA expression profiles in CD34+ bone marrow cells from patients with myelodysplastic syndrome

et al. 2010

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MicroRNAs (miRNAs) are small non-coding RNAs functioning as regulators of hematopoiesis. Their differential expression patterns have been linked with various pathological processes originating from hematopoietic stem cells (HSCs). However, limited information is available regarding the role of miRNAs in myelodysplastic syndrome (MDS). Using miRNA arrays, we measured expression of 1,145 miRNAs in CD34+ bone marrow cells obtained from 39 MDS and acute myeloid leukemia (AML) evolved from MDS patients, and compared them with those of six healthy donors. Differential miRNA expression was analyzed and a panel of upregulated (n¼13) and downregulated (n¼9) miRNAs were found (Po0.001) in MDS/AML patients. An increased expression of a large miRNA cluster mapped within the 14q32 locus was detected. Differences in miRNA expression of MDS subtypes showed a distinction between early and advanced MDS; an apparent dissimilarity was observed between RAEB-1 and RAEB-2 subtypes. In early MDS, we monitored upregulation of proapoptotic miR-34a, which may contribute to the increased apoptosis of HSCs. Patients with 5q deletion were characterized by decreased levels of miR-143* and miR-378 mapped within the commonly deleted region at 5q32. This is an early report describing differential expression in MDS CD34+ cells, likely reflecting their disease-specific regulation.

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Section: Discussionmentioning

confidence: 99%

Distinctive microRNA expression profiles in CD34+ bone marrow cells from patients with myelodysplastic syndrome

et al. 2010

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“…miR-342 has been shown to stimulate granulocytic differentiation (De Marchis et al, 2009). Interestingly, the putative target of miR-342 MEIS1, a member of the TALE family of homeodomain Differentially expressed miRNAs in APL patients S Careccia et al genes, has been shown to have a pivotal role in normal hematopoiesis (Abramovich and Humphries, 2005;Diaz-Blanco et al, 2007) and it is frequently upregulated in human AMLs (Kumar et al, 2009). Finally, it is known the involvement of let-7 family members in differentiation and development, as well as in antiproliferative functions, by targeting the RAS oncogene and the non-histone DNA binding protein HMGA2 (Johnson et al, 2005;Peng et al, 2008).…”

Section: Differentially Expressed Mirnas In Apl Patientsmentioning

confidence: 99%

A restricted signature of miRNAs distinguishes APL blasts from normal promyelocytes

Careccia¹,

Mainardi

Pelosi³

et al. 2009

Oncogene

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MicroRNAs (miRNAs) are small non-coding RNAs involved in the regulation of critical cell processes such as apoptosis, cell proliferation and differentiation. A small set of miRNAs is differentially expressed in hematopoietic cells and seemingly has an important role in granulopoiesis and lineage differentiation. In this study, we analysed, using a quantitative real-time PCR approach, the expression of 12 granulocytic differentiation signature miRNAs in a cohort of acute promyelocytic leukemia (APL) patients. We found nine miRNAs overexpressed and three miRNAs (miR-107, -342 and let-7c) downregulated in APL blasts as compared with normal promyelocytes differentiated in vitro from CD34 þ progenitors. Patients successfully treated with all-trans-retinoic acid (ATRA) and chemotherapy showed downregulation of miR-181b and upregulation of miR-15b, -16, -107, -223, -342 and let-7c. We further investigated whether the APL-associated oncogene, promyelocytic leukemia gene (PML)/retinoic acid receptor a (RARa), might be involved in the transcriptional repression of miR-107, -342 and let-7c. We found that PML/RARa binds the regulatory sequences of the intragenic miR-342 and let-7c. In addition, we observed, in response to ATRA, the release of PML/ RARa paralleled by their transcriptional activation, together with their host genes, EVL and C21orf34a. In conclusion, we show that a small subset of miRNAs is differentially expressed in APL and modulated by ATRA-based treatment.

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“…56 Of the distinct clusters, A, B and C, but not D, are thought to be important for normal hematopoiesis. 57 Gene ablation studies have shown specifically that Hoxa9, Hoxc8 and Hoxb6 are necessary for hematopoietic cells to progress though development. 57 In addition to their role in normal development, HOX genes also play roles in cell cycle control, cell adhesion and cell death.…”

Section: Role Of Calm-af10 Gene Fusion In Acute Leukemia D Caudell Anmentioning

confidence: 99%

The role of CALM–AF10 gene fusion in acute leukemia

Caudell

Aplan

2007

Leukemia

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Chromosomal translocations are important genetic perturbations frequently associated with hematologic malignancies; characterization of these events has been a rich source of insights into the mechanisms that lead to malignant transformation. The t(10;11)(p13;q14-21) results in a recently identified rare but recurring chromosomal translocation seen in patients with ALL as well as AML, and results in the production of a CALM-AF10 fusion gene. Although the details by which the CALM-AF10 fusion protein exerts its leukemogenic effect remain unclear, emerging data suggests that the CALM-AF10 fusion impairs differentiation of hematopoietic cells, at least in part via an upregulation of HOXA cluster genes. This review discusses the normal structure and function of CALM and AF10, describes the spectrum of clinical findings seen in patients with CALM-AF10 fusions, summarizes recently published CALM-AF10 mouse models and highlights the role of HOXA cluster gene activation in CALM-AF10 leukemia.

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Hox regulation of normal and leukemic hematopoietic stem cells

Cited by 141 publications

References 97 publications

Distinctive microRNA expression profiles in CD34+ bone marrow cells from patients with myelodysplastic syndrome

Distinctive microRNA expression profiles in CD34+ bone marrow cells from patients with myelodysplastic syndrome

A restricted signature of miRNAs distinguishes APL blasts from normal promyelocytes

The role of CALM–AF10 gene fusion in acute leukemia

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