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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acquired reciprocal chromosomal translocations that involve chromosome bands 5q31-33 are associated with a significant minority of patients with BCR-ABL-negative chronic myeloid leukemias. The most common abnormality is the t(5;12)(q33;p13), which fuses the ETV6/TEL gene to the platelet-derived growth factor receptor-beta (PDGFRB), a receptor tyrosine kinase that maps to 5q33. PDGFRB is disrupted by other translocations and to date four additional partner genes (H4, HIP1, CEV14 and Rab5) have been reported. Clinically, most patients present with a myeloproliferative disorder (MPD) with eosinophilia, eosinophilic leukemia or chronic myelomonocytic leukemia and thus fall into the broader category of myeloproliferative disorders/myelodysplastic syndromes (MPD/MDS). With the advent of targeted signal transduction therapy, patients with rearrangement of PDGFRB might be better classified as a distinct subgroup of MPD/MDS.
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PMID:Myeloproliferative disorders with translocations of chromosome 5q31-35: role of the platelet-derived growth factor receptor Beta. 1191 93

Flow cytometry is the primary tool for phenotyping leukemias and related conditions. With the ever increasing numbers of antibodies commercially available, the ability to study and understand leukemias, myelodysplastic syndromes, and the myelodysplastic/myeloproliferative diseases is improving. Although the data generated by flow cytometry are not comprehensive enough to completely subtype leukemias or myelodysplastic syndromes into their myriad divisions, this wealth of information does provide phenotype, reproducible enumeration of blasts, certain prognostic information, and it can reveal the presence of cell populations with aberrant antigen profiles. An important drawback to flow cytometry as it is performed today is the inability to look at the cells that mark with the antibody panels used. As classifications of leukemia and related conditions evolve, flow cytometry continues to answer many of the questions asked and to provide critical information reliably and quickly.
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PMID:Acute myeloid leukemia and related conditions. 1209 74

Of the myeloproliferative/myelodysplastic disorders (MPD/MDS) that occur in childhood most, regarding the cytogenetic and molecular genetic basis, is known about the two purely paediatric disorders: juvenile myelomonocytic leukaemia (JMML) and transient myeloproliferative disorder (TMD). Although much has been published about these two disorders, their aetiology is by no means fully established. It would appear, however, that in this paediatric subset of MPDs a stage/developmentally specific vulnerability for proliferation and transformation exists. The study of the molecular basis of many other MPD-like syndromes that also occur in childhood, has been greatly accelerated by the identification of rare, but recurring, cytogenetic abnormalities involving 8p11 and 5q31-33. Good collaborative studies could result in similar progress being made in the understanding of JMML and TMD.
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PMID:Cytogenetic and molecular genetic aspects of childhood myeloproliferative/myelodysplastic disorders. 1243 14

The important cell cycle regulatory gene p15(INK4b) has been shown to be inactivated in acute myeloid leukemia and myelodysplastic syndrome. Little is known about the expression and epigenetic modification of this gene in chronic myelomonocytic leukemia (CMML) that belongs to the myelodysplastic/myeloproliferative disorders (MDS/MPD) with a high proportion of blastic transformation. Analysis of bone marrow trephines in a series of 33 CMML cases showed an aberrant p15(INK4b) gene methylation in up to 58% of cases. Methylation was analyzed employing different methylation-specific PCR and genomic sequencing protocols. It turned out to be spread over a broad area of the 5' region and exhibited substantial heterogeneity between cases and even in individual patients. The degree of aberrant methylation was correlated with a reduced mRNA as well as reduced protein expression, and was associated with a higher expression of DNA methyltransferase DNMT 3A. We conclude that aberrant gene methylation is a frequent event in CMML that might contribute to the pathogenesis of this MDS/MPD.
Leukemia 2003 May
PMID:Aberrant methylation and impaired expression of the p15(INK4b) cell cycle regulatory gene in chronic myelomonocytic leukemia (CMML). 1275 Jul 5

The new WHO classification is based on the principles of REAL classification of lymphoma and expands to myeloid, mast cell and histiocytic/dendritic neoplasms. The distinct diseases are defined according to a combination of morphology, immunophenotype, genetic features, and clinical syndromes, and the cell origin is postulated. Lymphatic leukemia is included in lymphoma. The lymphoid malignancies are grouped into B cell lymphoma, T/NK cell lymphoma and Hodgkin lymphoma, and the myeloid neoplasm are grouped into 4 categories; chronic myeloproliferative diseases(chronic myelogeneous leukemia, polycythemia vera, chronic idiopathic myelofibrosis, essential thrombocythemia etc.), myelodysplastic/myeloproliferative diseases (chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia etc.), myelodysplastic diseases(perfactory anemia, refractory anemia with ringed sideroblasts etc.) and acute myeloid leukemia.
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PMID:[Malignant lymphoma and leukemia concepts in new WHO classification]. 1367 44

The 8p11 myeloproliferative syndrome (EMS) also known as stem cell leukemia-lymphoma syndrome (SCLL) is associated with translocations that disrupt FGFR1. The resultant fusion proteins are constitutively active tyrosine kinases, and different FGFR1 fusions are associated with subtly different disease phenotypes. We report here a patient with a t(8;17)(p11;q23) and an unusual myelodysplastic/myeloproliferative disease (MDS/MPD) characterized by thrombocytopenia due to markedly reduced size and numbers of megakaryocytes, with elevated numbers of monocytes, eosinophils and basophils. A novel mRNA fusion between exon 32 of the myosin XVIIIA gene (MYO18A) at chromosome band 17q11 and exon 9 of FGFR1 was identified. Partial characterization of the genomic breakpoints in combination of bubble-PCR with fluorescence in situ hybridization revealed that the t(8;17) arose from a three-way translocation with breaks at 8p11, 17q11 and 17q23. MYO18A-FGFR1 is structurally similar to other fusion tyrosine kinases and is likely to be the causative transforming lesion in this unusual MDS/MPD.
Leukemia 2005 Jun
PMID:The t(8;17)(p11;q23) in the 8p11 myeloproliferative syndrome fuses MYO18A to FGFR1. 1580 Jun 73

The PRAME (preferentially expressed antigen of melanoma) gene has been shown to be expressed in high levels in some solid tumors and hemopoietic neoplasias but not or only weakly expressed in normal tissues. It encodes an antigen recognized by autologous cytolytic T lymphocytes. PRAME is a good candidate for tumor immunotherapy and is a useful marker gene for detection of minimal residual disease (MRD). In this study, PRAME mRNA using real-time RT-PCR was studied in 74 adult cases with acute leukemia-68 had de-novo acute leukemia, 3 had chronic myeloid leukemia-blastic crisis (CML-BC), and 3 had myelodysplastic/myeloproliferative syndrome-blastic transformation (MDS/MPD-BT)-and the results were compared with 30 age-matched healthy volunteers. Nineteen of 74 cases with leukemia expressed PRAME, while only 2 controls showed weak expression. The prevalence of PRAME expression in AML and ALL cases was 30% and 17%, respectively. We did not find any important correlation between PRAME expression and clinical characteristics, such as age, sex, organomegaly/lymphadenopathy, Hb, WBC count, platelet count, LDH level, alkaline phosphatase, albumin, cell-surface antigens, response to therapy, or progression-free and overall survival. PRAME was monitored in 15 cases during remission and/or relapse. There was a good correlation between PRAME mRNA and hematological remission and/or relapse. Interestingly, PRAME was very high in one case with AML but was not found 3 months after allogeneic transplantation. PRAME mRNA is observed in about one-third of AML cases; it may be a useful marker to detect MRD, and it may also be a good predictor for the timing of donor lymphocyte infusions (DLI) in the post-transplant period in cases of molecular relapse.
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PMID:PRAME mRNA levels in cases with acute leukemia: clinical importance and future prospects. 1604 53

We report on a patient fulfilling the diagnostic criteria of unclassifiable myelodysplastic/myeloproliferative diseases with prominent erythropoietic hyperplasia/dysplasia (erythroid preleukemia) and the unique translocation (8;9)(p23;p24). The patient presented with B-symptoms, erythroblastemia, thrombopenia, marked eosinophilia, presence of myeloid precursors in the peripheral blood, and decreased erythropoietin level. Nodular peritrabecular polymorphous blasts, dysplastic megakaryocytes, and a diffuse argyrophilic fibrosis were detected in the trephine bone marrow biopsy. Immunohistochemically, the blasts stained positively for glycophorin C and hemoglobin A; the proliferation fraction was nearly 90% in the Ki-67 stain. Expression of the phosphorylated Janus kinase 2 was detected in almost all megakaryocytes and in isolated erythroblast islets, suggesting a probable activation of Janus kinase 2, the jak-2 gene being mapped on 9p24. Ten months after initial diagnosis, the disease progressed to frank acute erythroid leukemia. We report for the first time a myelodysplastic/myeloproliferative disease (erythroid preleukemia) accompanied by the specific chromosomal aberration t(8;9)(p23;p24), distinct histopathology, and clinical and laboratory symptoms, and progress to acute erythroid leukemia.
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PMID:Myelodysplastic/myeloproliferative disease with erythropoietic hyperplasia (erythroid preleukemia) and the unique translocation (8;9)(p23;p24): first description of a case. 1656 30

A mutation in the JH2 pseudokinase domain of the Janus kinase 2 gene (JAK2 V617F) has been described in chronic myeloproliferative disorders (MPD). We screened 79 acute myeloid leukemia (AML) cell lines and found five positive for JAK2 V617F (HEL, MB-02, MUTZ-8, SET-2, UKE-1), 4/5 with histories of MPD/MDS. While SET-2 expressed both mutant (mu) and wild-type (wt) JAK2, remaining positives carried homo-/hemizygous JAK2 mutations. Microsatellite analysis confirmed losses of heterozygosity (LOH) affecting the JAK2 region on chromosome 9p in MB-02, MUTZ-8 and UKE-1, but also in HEL, the only JAK2mu cell line lacking any reported MPD/MDS history. All five JAK2mu cell lines displayed cytogenetic hallmarks of MDS, namely losses of 5q or 7q, remarkably in 4/5 cases affecting both chromosomes. Our combined FISH and microsatellite analysis uncovered a novel mechanism to supplement mitotic recombination previously proposed to explain JAK2 LOH, namely chromosome deletion with/without selective JAK2mu amplification. Confirming the importance of the mutated JAK2 protein for growth and prevention of apoptosis, JAK2mu cell lines displayed higher sensitivities to JAK2 inhibition than JAK2wt cell lines. In summary, JAK2 V617F cell lines, derived from patients with history of MPD/MDS, represent novel research tools for elucidating the pathobiology of this JAK2 mutation.
Leukemia 2006 Mar
PMID:JAK2 V617F tyrosine kinase mutation in cell lines derived from myeloproliferative disorders. 1640 98

The 2001 World Health Organization (WHO)-sponsored classification of hematopoietic tumors has, for the first time, clearly defined a group of rare myeloid neoplasms termed myelodysplastic/myeloproliferative diseases (MDS/MPDs). This group includes three main entities, chronic myelomonocytic leukemia, atypical chronic myeloid leukemia and juvenile myelomonocytic leukemia, and also several less well defined, 'unclassifiable' disorders with MDS/MPN-like features. In the upcoming fourth edition of the WHO fascicle, due out later this year, the term 'MPD' is replaced by 'myeloproliferative neoplasm (MPN)'. Accordingly, the term MDS/MPD is being replaced by 'MDS/MPN' that will be used in this review. Although much progress has been made in understanding the molecular pathogenesis of myeloid neoplasms, most of the diseases included in the group of MDS/MPN still remain 'clinicopathologically assigned'. In other words, they can only be accurately categorized by a careful multiparametric approach that is based on the integration of bone marrow and peripheral blood morphology with other laboratory and clinical findings. The current 'spotlight' review provides practical guidelines, which should allow for a reproducible classification of these uncommon neoplasms when encountered in clinical practice.
Leukemia 2008 Jul
PMID:The myelodysplastic/myeloproliferative neoplasms: myeloproliferative diseases with dysplastic features. 1848 Aug 33


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