The maximal nuclear and cell body diameters of leukaemic agranular myeloblasts ("type 1" without azurophilic granules) were measured in bone marrow smears of patients suffering from acute myeloblastic leukaemia with minimal differentiation (M0 AML), without and with maturation (M1 and M2 AML), refractory anaemia with excess of myeloblasts (RAEB) and chronic phase of the myeloid leukaemia (CML) to provide more information on the cytoplasmic space estimate occupied by the nucleus. The largest size of the cytoplasmic space occupied by the nucleus in agranular myeloblasts was noted in M0 and M1 AML in comparison with M2 AML or RAEB, and especially with CML. Similarly, agranular myeloblasts with nuclear bodies occupying more than 90 per cent of the cell space were most frequent in M0 and M1 AML (> 50 %), less frequent in M2 and RAEB (~ 20 %) but very rare in CML (~ 5 %). According to electron microscopy, the very narrow cytoplasmic shell surrounding the nucleus in such myeloblasts did not possess any space for structural components characteristic of the granulocytic cell lineage. Thus, the basic morphology of these myeloblasts would correspond to morphological features of a less differentiated committed stem cell. It should be noted that such cells may be easily recognized in currently stained bone marrow or peripheral blood smears.
- MeSH
- akutní myeloidní leukemie * patologie MeSH
- buněčná diferenciace * MeSH
- chronická myeloidní leukemie * patologie MeSH
- cytoplazma * metabolismus MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- myelodysplastické syndromy * patologie MeSH
- prekurzorové buňky granulocytů patologie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Patients with myelodysplastic neoplasms (MDS) are classified according to the risk of acute myeloid leukemia transformation. Some lower-risk MDS patients (LR-MDS) progress rapidly despite expected good prognosis. Using diagnostic samples, we aimed to uncover the mechanisms of this accelerated progression at the transcriptome level. RNAseq was performed on CD34+ ribodepleted RNA samples from 53 LR-MDS patients without accelerated progression (stMDS) and 8 who progressed within 20 months (prMDS); 845 genes were differentially expressed (ІlogFCІ > 1, FDR < 0.01) between these groups. stMDS CD34+ cells exhibited transcriptional signatures of actively cycling, megakaryocyte/erythrocyte lineage-primed progenitors, with upregulation of cell cycle checkpoints and stress pathways, which presumably form a tumor-suppressing barrier. Conversely, cell cycle, DNA damage response (DDR) and energy metabolism-related pathways were downregulated in prMDS samples, whereas cell adhesion processes were upregulated. Also, prMDS samples showed high levels of aberrant splicing and global lncRNA expression that may contribute to the attenuation of DDR pathways. We observed overexpression of multiple oncogenes and diminished differentiation in prMDS; the expression of ZEB1 and NEK3, genes not previously associated with MDS prognosis, might serve as potential biomarkers for LR-MDS progression. Our 19-gene DDR signature showed a significant predictive power for LR-MDS progression. In validation samples (stMDS = 3, prMDS = 4), the key markers and signatures retained their significance. Collectively, accelerated progression of LR-MDS appears to be associated with transcriptome patterns of a quiescent-like cell state, reduced lineage differentiation and suppressed DDR, inherent to CD34+ cells. The attenuation of DDR-related gene-expression signature may refine risk assessment in LR-MDS patients.
- MeSH
- buněčná adheze MeSH
- buněčný cyklus MeSH
- kinasy NEK genetika metabolismus MeSH
- lidé MeSH
- myelodysplastické syndromy * genetika MeSH
- nádory * MeSH
- oprava DNA MeSH
- transkriptom MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Akutní promyelocytární leukemie (APL) patří mezi vzácná nádorová onemocnění. Charakteristickým znakem je závažná získaná porucha krevního srážení. Vznik a vývoj onemocnění je v 99 % spojený s reciprokou translokací genu pro receptor kyseliny alfa-retinové (RARα) z chromosomu 17 na chromosom 15, do oblasti genu označovaného promyelocytic leukemia gene (PML). Touto translokací vzniká na chromosomu 15 leukemický fúzní gen PML/RARα. Gen RARα výjimečně fúzuje s jinými variantními geny než PML. V tomto článku je uveden případ APL s variantní RARα translokací, zaměřený na morfologické nálezy.
Acute promyelocytic leukemia (APL) is a rare disease. APL is frequently associated with disseminated intravascular coagulation and increased fibrinolysis. The origin and development of the disease is 99 % associated with the reciprocal translocation of the alpha-retinoic acid (RARα) gene from chromosome 17 on chromosome 15 to the region of the gene called the promyelocytic leukemia gene (PML). The result of this translocation is the PML/RARα fusion gene. In less than 1%, the RARα gene fuses with other variant genes than PML. This article presents the case of APL with variant RARα translocation, focused on morphological findings.
- MeSH
- akutní promyelocytární leukemie * diagnóza MeSH
- buňky kostní dřeně patologie MeSH
- cytologické techniky MeSH
- dospělí MeSH
- fúze genů MeSH
- histologické techniky MeSH
- krevní buňky patologie MeSH
- lidé MeSH
- odmítnutí terapie pacientem MeSH
- recidiva MeSH
- translokace genetická * MeSH
- vyšetřování kostní dřeně MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
