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It has become important to be careful in terms of side effects with the increased lenalidomide use. The most commonly reported adverse events with the use of lenalidomide were hematologic toxicities and less frequently peripheral edema, infections, gastrointestinal disorders, fatigue, and muscle cramps. In particular, the nonserious rash is the most common cause of permanent discontinuation of lenalidomide. Although morbilliform, urticarial, or acneiform rashes have been observed with lenalidomide, malar rash-like lesions have not been described previously. Our aim is to present here 71-year-old female myelodysplastic syndrome patient with deletion of 5q abnormality who should be discontinued lenalidomide due to recurrent skin reaction like a malar rash.

Myelodysplastic syndrome is a heterogeneous group of acquired malignant diseases of the clones. Its basic clinical features are that the hematopoietic cells in the bone marrow have abnormal morphological manifestations and the reduction of the three-line blood cells in the peripheral blood, and high risk of conversion to acute myeloid leukemia. The differential diagnosis of MDS, to assess the prognosis of treatment decisions are of great significance. In recent years, epigenetic pathway participates in the etiology and pathogenesis of MDS, especially micro RNA plays an important role in the occurrence, development and prognosis of MDS. This article expounds the significance and status of related miRNA research through the relationship between the clinical monitorability of miRNA and blood diseases; and focus on the miRNAs that may play an important role in the diagnosis and clinical progress of MDS, as well as the expression of miRNAs that are specific to miR145 and miR146 a in 5 q-syndrome. With a view to be able to carry out more in-depth research and exploration on this basis, miRNA in the clinical diagnosis and treatment of myelodysplastic syndrome play more potential. [ABSTRACT FROM AUTHOR]

The authors present a case of a 60-year-old patient with incidentally uncovered significant macrocytic anaemia and thrombocytosis. Myelodysplastic syndrome, namely 5q- syndrome was diagnosed. From the beginning, the patient was dependent on red blood cell transfusions. Chelation was initially successful, but later it failed especially due to the patient's non compliance. At the time when treatment with lenalidomide was clearly indicated, it was not possible to obtain this medication. At 53 months from diagnosis, the disease progressed to RAEB. The patient died of liver and renal failure without developing acute leukaemia. Severe hemosiderosis of the organs, especially the liver and heart, was one of the causes of death. The article includes the autopsy report and photographs of the relevant histological slides, showing hemosiderosis of the vital organs and pathological-anatomical changes that led to their failure. The paper shows severe organ damage that occurs in patients with untreated iron overload. However, haematologists can currently prevent fatal organ damage in long-term transfused patients suffering from myelodysplastic syndrome with the aid of timely and consistent iron chelator therapy and by attempting to eliminate the dependence on transfusions using erythropoietin or in case of its failure by administering lenalidomide. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) represent a heterogeneous group of acquired clonal hematopoietic disorders characterized by peripheral blood cytopenias, paradoxical BM hypercellularity, ineffective hematopoiesis, and increased risk of leukemic transformation. Risk stratification, using different prognostic scores and markers, is at the core of MDS management. Deletion 5q [del(5q)] MDS is a distinct class of MDS characterized by the haploinsufficiency of specific genes, microRNAs, and proteins, which has been linked to increased sensitivity to the drug lenalidomide. Phase II and III clinical trials have demonstrated the efficacy of lenalidomide in improving clinical outcomes of patients with del(5q) MDS, including reduction in red blood cell transfusion requirements and improvements in quality of life. Lenalidomide has also demonstrated some activity in non-del(5q) lower-risk MDS as well as higher-risk MDS, especially in combination with other agents. In this paper, we review the pathogenesis of del(5q) MDS, the proposed mechanisms of action of lenalidomide, the major clinical trials that documented the activity of lenalidomide in different MDS populations, potential predictors of benefit from the drug and suggested mechanisms of resistance, and the use of combination strategies to expand the clinical utility of lenalidomide in MDS. [ABSTRACT FROM AUTHOR]

Abstract In this case, a 78-year-old woman presents with macrocytosis and fatigue. It was developed from the early stage of the disease (and the work-up for cause of macrocytosis) and includes a teaching of megaloblastic and nonmegaloblastic causes for macrocytosis. The case follows a diagnosed patient with early stage myelodysplastic syndrome which progresses into acute leukemia. New classifications and staging of the disease is addressed. Our purpose is to provide standardized peer-reviewed virtual cases for teaching hematology to 2nd-year medical students and to provide course directors a resource for use in their medical school. This resource also provides access to images from the American Society of Hematology image bank, as well as contributions from members and images from my own personal collection. Feedback from our course directors’ annual meeting has helped us develop the updates and revisions.

Myelodysplastic syndrome (MDS) is a pre-cancerosis, or rather a pre-leukaemic state. It is not a definitive disease but rather involves heterogeneous clinical manifestations ranging from cytopenias to conditions similar to acute myeloid leukaemia. This characteristic of MDS explains the difficulty of elucidating its pathogenesis. Admirable progress regarding cell structure and metabolism as well as cell growth regulation has extended our understanding of MDS pathogenesis. Recently, two interesting findings in the pathogenesis of 5q-syndrome and refractory anaemia with ringed side-roblasts (RARS) have been reported. In 5q-syndrome, ribosomal stress has been identified as the underlying mechanism of refractory anaemia. It has also been partially explained why ribosomal stress does not hamper effective megakary-opoiesis in this MDS subtype. In the majority of RARS patients, a mutation of the SF3B1 gene, which plays a role in pre-mRNA splicing, has been uncovered. The contribution of this SF3B1 mutation to the development of ringed side-roblasts and its role in iron metabolism within erythroblasts represent an impulse for further research. SF3B1 mutation in chronic lymphocytic leukaemia as opposed to RARS is associated with poor prognosis. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis presenting with peripheral cytopenias in combination with a hyperplastic bone marrow and an increased risk of evolution to acute myeloid leukemia. The classification systems such as the WHO classification mainly rely on morphological criteria and are supplemented by the International Prognostic Scoring System which takes cytogenetical changes into consideration when determining the prognosis of MDS but wide intra-subtype variations do exist. The pathomechanisms causing primary MDS require further work. Development and progression of MDS is suggested to be a multistep alteration to hematopoietic stem cells. Different molecular alterations have been described, affecting genes involved in cell-cycle control, mitotic checkpoints, and growth factor receptors. Secondary signal proteins and transcription factors, which gives the cell a growth advantage over its normal counterpart, may be affected as well. The accumulation of such defects may finally cause the leukemic transformation of MDS. [ABSTRACT FROM AUTHOR]

Alternative pre-mRNA splicing alters gene expression and protein function, and aberrant splicing patterns can be associated with neoplasia. The potential role of disordered RNA splicing in myelodysplastic syndrome (MDS) is unexplored. We analysed the splicing repertoire of CDC25C- a gene localised to chromosome 5q31 and encoding a cyclin/cyclin-dependent-kinase regulatory phosphatase critical for cell cycle checkpoint control - in MDS, acute myeloid leukemia, chronic lymphocytic leukemia and healthy tissues. Five novel splicing isoforms were detected, and the splicing patterns were generally distinct in neoplastic samples compared with healthy controls. One of the novel isoforms, which we have termed CDC25C-6, occurred in 58% of the samples in our cohort. The results of this study suggest the possibility of aberrant splicing contributing to the phenotype in MDS and other haematologic malignancies. [ABSTRACT FROM AUTHOR]

The 5q-syndrome is a distinct hematological disorder with typical laboratory, morphological, cytogenetic, molecular and prognostic features. It is defined as a myelodysplastic syndrome with a medullary blast count < 5% and an isolated interstitial deletion of the long arm of chromosome 5, including bands q31-q33. The molecular basis of this disease has not yet been fully elucidated, but there is evidence that a commonly deleted region of 1.5 Mb harbors one or several tumor suppressor genes, the loss of which being the basic event leading to disease activity. The Sqe deletion has been demonstrated in very early hematopoietic precursors, including CD34+CD133+ and CD34+CD38-Thyl+ cells. Analysing data of 60 patients with the 5q-syndrome that were followed over a period of up to 28 years, we found a median age at diagnosis of 66.8 years and a female preponderance with a male to female ratio of 1:1.5. Anemia is usually macrocytic and combined with low reticulocyte counts and high erythropoetin levels. Three types of cytogenetic deletion are most prevalent: del(s) (q13q33), del(5)(q13q31) and del(5)(q22q33). The Sqe syndrome has a good prognosis with a median overall survival of 107 months at a median follow-up of 53 months, and a low probability of transformation to AML An increase of the medullary blast count to ≥ 5°/o or the addition of one karyotypic anomaly severely reduces median overall survival. The most promising therapeutic approach is the novel thalidomide analogue CC5013 that is currently evaluated in an international phase II study. [ABSTRACT FROM AUTHOR]

The myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal disorders of the haematopoietic stem cell and primarily involve cells of the myeloid lineage. Using cDNA microarrays comprising 6000 human genes, we studied the gene expression profiles in the neutrophils of 21 MDS patients, seven of which had the 5q- syndrome, and two acute myeloid leukaemia (AML) patients when compared with the neutrophils from pooled healthy controls. Data analysis showed a high level of heterogeneity of gene expression between MDS patients, most probably reflecting the underlying karyotypic and genetic heterogeneity. Nevertheless, several genes were commonly up or down-regulated in MDS. The most up-regulated genes included RAB20, ARG1, ZNF183 and ACPL. The RAB20 gene is a member of the Ras gene superfamily and ARG1 promotes cellular proliferation. The most down-regulated genes include COX2, CD18, FOS and IL7R. COX2 is anti-apoptotic and promotes cell survival. Many genes were identified that are differentially expressed in the different MDS subtypes and AML. A subset of genes was able to discriminate patients with the 5q- syndrome from patients with refractory anaemia and a normal karyotype. The microarray expression results for several genes were confirmed by real-time quantitative polymerase chain reaction. The MDS-specific expression changes identified are likely to be biologically important in the pathophysiology of this disorder. [ABSTRACT FROM AUTHOR]

The WHO classification of hematological malignancies includes 5q-syndrome as a separate category within myelodysplastic syndromes (MDS). Clinically, patients with 5q-syndrome have a milder disease than patients with other MDS. The basis for this difference is not known. Identifying 5q-syndrome can be difficult because some of its morphologic and cytogenetic features are similar to those of other MDS. We compared apoptosis between 5q-syndrome and other refractory anemias. We found lower levels of apoptosis in 5q-syndrome as detected by less disruption of mitochondrial potential (P=0.008) and decreased annexin V positivity (P=0.01). Our results suggest that lower apoptosis in 5q-syndrome may explain the milder clinical course of the disease and distinguish 5q-syndrome from other MDS. [Copyright &y& Elsevier]

Abstract: The 2008 World Health Organization (WHO) proposed revision of the classification of MDS recognizes a deletion (5q) subtype with mutation of Janus kinase-2 (JAK2V617F). We investigated the clonal origin of this gene mutation in a patient with del(5q) MDS presenting with thrombocytosis and normal hemoglobin. Analysis of colony forming units-granulocyte-monocyte (CFU-GM) and erythropoietin-independent growth of bone marrow (BM) and peripheral blood (PB) burst forming units-erythroid (BFU-E) showed that del(5q) and JAK2V617F existed in progenitors derived from independent clones. Fifty percent of endogenous erythroid colonies (EEC) harbored the JAK2V617F mutation whereas fluorescent in situ hybridization (Fish) with a chromosome 5 (q31.1) probe showed only a diploid allele compliment. Assessment of transcriptional clonality by iduronate-2-sulfatase (IDS) gene polymorphism suggested that JAK2V617F was acquired in at least two independent multipotent stem cell progeny. Our findings indicate that JAK2V617F mutant clones may arise in genetically discordant clones independent of del(5q). [Copyright &y& Elsevier]

JAK2 V617F mutation is mostly seen in BCR-ABLI negative myeloproliferative neoplasms. Among other myeloid neoplasms, it occurs with remarkably high frequency in refractory anemia with ring sideroblasts associated with marked thrombocytosis, a group of myeloid neoplasms with both dysplastic and proliferative features. It has also been reported in occasional cases of myelodysplastic syndrome with isolated del(5q), often with a diagnosis of refractory cytopenia with multilineage dysplasia. We performed a retrospective analysis of JAK2 V617F mutation in Chinese patients with myeloid neoplasms and isolated del(5q), and were able to demonstrate the frequent occurrence of JAK2 V617F mutation in 5q- syndrome. [ABSTRACT FROM AUTHOR]