ABSTRACT
Generally, clefted lymphocytes can mainly occur in patients with Bordetella pertussis infection, follicular lymphoma, or less commonly in chronic lymphocytic leukemias. The presence of cleaved leukemic blast cells in cases with AML is quite rare. Additionally, in the absence of typical morphological findings (including blasts with hemophagocytosis, eosinophilia and micromegakaryocytes) in AML with TLS::ERG, the occurrence of cleaved blast cells, as well as vacuolation and cytoplasmic pseudopod formation in the present case is extremely uncommon. Moreover, CD56 expression in AML with t(16;21) has been suggested to connect with a poor prognosis, and may influence the CR duration and overall survival. Our present case presented partial expression of CD56 and bone marrow reexamination showed continuous CR for three months, but due to economic reasons, he did not continue follow-up examination, and the efficacy could not be evaluated. In brief, this case reminds us to recognize atypical morphologic features of clefted leukemic blasts and pseudopodia-like cytoplasmic projections in some subtypes of leukemias.
Subject(s)
Bacteremia , Fungemia , Humans , Fungemia/diagnosis , Bacteremia/diagnosis , Early DiagnosisSubject(s)
Leukemia, Myeloid, Acute , Lymphohistiocytosis, Hemophagocytic , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/etiology , Core Binding Factor Alpha 2 Subunit/genetics , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/genetics , Translocation, Genetic , RUNX1 Translocation Partner 1 Protein/geneticsSubject(s)
Osteomyelitis , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , DNA-Binding Proteins/genetics , Gene Fusion , Oncogene Proteins, Fusion/genetics , Osteomyelitis/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Trans-Activators/genetics , Transcription Factors/genetics , Female , ChildSubject(s)
HIV Infections , Mycoses , Child , Humans , HIV Infections/complications , Mycoses/complicationsABSTRACT
Zinc finger protein 521 (Zfp521), a quiescent hematopoietic stem cell (HSC)-enriched transcription factor, is involved in the self-renewal and differentiation of fetal liver HSC. However, its role in adult hematopoiesis remains elusive. Here, we found that Zfp521 deletion did not inhibit adult hematopoiesis under homeostatic conditions. In contrast, Zfp521-null chimeric mice showed significantly reduced pool size of HSC and hematopoietic progenitor cells associated with increased apoptosis and loss of quiescence. Competitive serial transplantation assays revealed that Zfp521 regulates HSC self-renewal and differentiation under regenerative stress. Mechanistically, Zfp521 transcriptionally repressed Rela expression by increasing H3K9ac and decreasing H3K9me3 levels in its promoter. Knockdown of Rela inhibited the hyper-activated NF-κB pathway and reversed the loss of quiescence in Zfp521-null HSC under stress. Thus, our results reveal a previously unrecognized role for Zfp521 as critical regulator of quiescence and self-renewal of HSC in adult hematopoiesis mediated at least partly by controlling Rela expression.
Subject(s)
Behcet Syndrome/drug therapy , Immunosuppressive Agents/therapeutic use , Intestinal Diseases/drug therapy , Myelodysplastic Syndromes/genetics , Thalidomide/therapeutic use , Trisomy , Behcet Syndrome/blood , Behcet Syndrome/genetics , Chromosomes, Human, Pair 8 , Female , Humans , Intestinal Diseases/blood , Intestinal Diseases/genetics , Middle Aged , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/diagnosis , Oral Ulcer/drug therapyABSTRACT
BACKGROUND: Zinc finger and BTB domain-containing protein 46 (Zbtb46) is a transcription factor identified in classical dendritic cells, and maintains dendritic cell quiescence in a steady state. Zbtb46 has been reported to be a negative indicator of acute myeloid leukemia (AML). We found that Zbtb46 was expressed at a relatively higher level in hematopoietic stem and progenitor cells (HSPCs) compared to mature cells, and higher in AML cells compared to normal bone marrow (BM) cells. However, the role of Zbtb46 in HSPCs and AML cells remains unclear. Therefore, we sought to elucidate the effect of Zbtb46 in normal hematopoiesis and AML cells. METHODS: We generated Zbtb46 and Zbtb46Mx1-Cre mice. The deletion of Zbtb46 in Zbtb46Mx1-Cre mice was induced by intraperitoneal injection of double-stranded poly (I). poly (C) (poly(I:C)), and referred as Zbtb46 cKO. After confirming the deletion of Zbtb46, the frequency and numbers of HSPCs and mature blood cells were analyzed by flow cytometry. Serial intraperitoneal injection of 5-fluorouracil was administrated to determine the repopulation ability of HSCs from Zbtb46 and Zbtb46 cKO mice. The correlation between Zbtb46 expression and prognosis was analyzed using the data from the Cancer Genome Atlas. To investigate the role of Zbtb46 in AML cells, we knocked down the expression of Zbtb46 in THP-1 cells using lentiviral vectors expressing small hairpin RNAs targeting Zbtb46. Cell proliferation rate was determined by cell count assay. Cell apoptosis and bromodeoxyuridine incorporation were determined by flow cytometry. RESULTS: The percentages and absolute numbers of HSPCs and mature blood cells were comparable in Zbtb46 cKO mice and its Zbtb46 littermates (Zbtb46vs. Zbtb46 cKO, HPC: 801,310â±â84,282 vs. 907,202â±â97,403, t = 0.82, P = 0.46; LSK: 86,895â±â7802 vs. 102,210â±â5025, tâ=â1.65, Pâ=â0.17; HSC: 19,753â±â3116 vs. 17,608â±â3508, tâ=â0.46, Pâ=â0.67). The repopulation ability of HSCs from Zbtb46Mx1-Cre mice was similar to those from Zbtb46 control (Pâ=â0.26). Zbtb46 had elevated expression in AML cells compared to total BM cells from normal control. Knockdown of Zbtb46 in THP-1 cells led to a significant increase in cell apoptosis and reduced cell growth and proliferation. CONCLUSION: Collectively, our data indicate that Zbtb46 is essential for survival and proliferation of AML cells, but dispensable for normal hematopoiesis.
