The translocation (6;9) (p23;q34) shows consistent rearrangement of two genes and defines a myeloproliferative disorder with specific clinical features

Abstract Translocation (6;9)(p23;q34) is a cytogenetic aberration that can be found in specific subtypes of both acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). This translocation is associated with an unfavourable prognosis. Recently, the genes involved in the t(6;9) were isolated and characterized. Breakpoints in both the dek gene on chromosome 6 and the can gene on chromosome 9 appear to occur in defined regions, which allows us to diagnose this type of leukemia at the molecular level. Moreover, because of the translocation a chimeric dek-can mRNA is formed which, as we show here, is an additional target for diagnosis via cDNA-preparation and the polymerase chain reaction (PCR). We studied 17 patients whose blood cells and/or bone marrow cells showed a t(6;9) with karyotypic analysis. Fourteen patients suffered from AML, one patient had a refractory anemia with excess of blasts in transformation (RAEBt), one patient had an acute myelofibrosis (AMF), and one patient a chronic myeloid leukemia (CML). In nine cases studies at the DNA and RNA levels were possible while in seven cases only the DNA could be analyzed. In one case only RNA was available. Conventional Southern blot analysis showed the presence of rearrangements of both the dek gene and the can gene. In both genes, breakpoints cluster in one intron in the patients investigated. The presence of a consistent chimeric dek-can product after cDNA preparation followed by the PCR was demonstrated. We conclude from our data that the t(6;9) is found in myeloproliferative disorders with typical clinical characteristics. This translocation results in highly consistent abnormalities at the molecular level.

Download Full-text

The translocation (6;9) (p23;q34) shows consistent rearrangement of two genes and defines a myeloproliferative disorder with specific clinical features

Blood ◽

10.1182/blood.v79.11.2990.bloodjournal79112990 ◽

1992 ◽

Vol 79 (11) ◽

pp. 2990-2997 ◽

Cited By ~ 1

Author(s):

D Soekarman ◽

M von Lindern ◽

S Daenen ◽

B de Jong ◽

C Fonatsch ◽

...

Keyword(s):

Myeloid Leukemia ◽

Bone Marrow Cells ◽

Molecular Level ◽

Myeloproliferative Disorders ◽

Chromosome 9 ◽

Refractory Anemia ◽

Karyotypic Analysis ◽

Cytogenetic Aberration ◽

Dna And Rna ◽

Cdna Preparation

Translocation (6;9)(p23;q34) is a cytogenetic aberration that can be found in specific subtypes of both acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). This translocation is associated with an unfavourable prognosis. Recently, the genes involved in the t(6;9) were isolated and characterized. Breakpoints in both the dek gene on chromosome 6 and the can gene on chromosome 9 appear to occur in defined regions, which allows us to diagnose this type of leukemia at the molecular level. Moreover, because of the translocation a chimeric dek-can mRNA is formed which, as we show here, is an additional target for diagnosis via cDNA-preparation and the polymerase chain reaction (PCR). We studied 17 patients whose blood cells and/or bone marrow cells showed a t(6;9) with karyotypic analysis. Fourteen patients suffered from AML, one patient had a refractory anemia with excess of blasts in transformation (RAEBt), one patient had an acute myelofibrosis (AMF), and one patient a chronic myeloid leukemia (CML). In nine cases studies at the DNA and RNA levels were possible while in seven cases only the DNA could be analyzed. In one case only RNA was available. Conventional Southern blot analysis showed the presence of rearrangements of both the dek gene and the can gene. In both genes, breakpoints cluster in one intron in the patients investigated. The presence of a consistent chimeric dek-can product after cDNA preparation followed by the PCR was demonstrated. We conclude from our data that the t(6;9) is found in myeloproliferative disorders with typical clinical characteristics. This translocation results in highly consistent abnormalities at the molecular level.

Download Full-text

Antibody recognition of the tumor-specific bcr-abl joining region in chronic myeloid leukemia.

Journal of Experimental Medicine ◽

10.1084/jem.169.1.87 ◽

1989 ◽

Vol 169 (1) ◽

pp. 87-98 ◽

Cited By ~ 46

Author(s):

J van Denderen ◽

A Hermans ◽

T Meeuwsen ◽

C Troelstra ◽

N Zegers ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Polyclonal Antiserum ◽

Chromosome 9 ◽

Leukemic Cells ◽

Kinase Assay ◽

Exon 2 ◽

Elisa System ◽

Antibody Recognition ◽

Dna And Rna

Chronic myeloid leukemia (CML) is characterized by the presence of a 210-kD protein (P210bcr-abl) in the cytoplasm of leukemic cells, generated by the reciprocal translocation between chromosome 9 and chromosome 22. Due to this translocation, the abl oncogene is coupled to the bcr gene, forming a new determinant in this protein encoded by the bcr-abl joining region. In the joining region itself, either the bcr exon 2 is coupled to the abl exon 2 (b2-a2), or the bcr exon 3 is coupled to the abl exon 2 (b3-a2). Thus, these joining regions form by definition new tumor-specific determinants in the respective chimeric P210-bcr-abl molecules. This paper addresses the question as to whether these tumor-specific joining regions are exposed on the P210bcr-abl molecule in such a way that antibodies can be generated to detect these sites. To test this possibility a polyclonal antiserum, termed BP-1, was raised against a synthetic peptide representative for the b2-a2 joining region. The reactivity of BP-1 was analyzed in an ELISA system on various synthetic peptides. Peptide inhibition studies showed the presence of antibodies to different parts of the b2-a2 peptide in the polyvalent antiserum. The reactivity of BP-1 was then tested with native P210bcr-abl molecules in various CML cell lines (K562, LAMA-84, and BV173) using a protein kinase assay. In this context, the bcr-abl junctions were first analyzed at the DNA and RNA level. The present study indicates that BP-1 specifically recognizes the b2-a2 junction in native P210bcr-abl. Furthermore, BP-1 clearly discriminates between b2-a2 P210bcr-abl and b3-a2 P210bcr-abl. We conclude that the tumor-specific b2-a2 joining region is antigenically exposed on the native P210bcr-abl molecule.

Download Full-text

NORMAL LIPOXYGENASE ACTIVITY IN ERYTHROMELALGIC THROMBOTIC THROMBOCYTHEMI

10.1055/s-0038-1643396 ◽

1987 ◽

Author(s):

J J Michiels ◽

E Haddeman

Keyword(s):

Bone Marrow ◽

Chromosomal Abnormalities ◽

Bone Marrow Cells ◽

Myeloproliferative Disorders ◽

Lipoxygenase Activity ◽

Chromosome 9 ◽

Eicosatetraenoic Acid ◽

Myeloproliferative Disease ◽

Giant Platelets ◽

Myeloid Metaplasia

It has been suggested that a selective lipoxygenase deficiency may be a mechanism for hyperfunction of platelets in myeloproliferative disorders. 24 out of 60 patients with one of the myeloproliferative disorders polycythemia vera, myeloid metaplasia and myelofibrosis, essential thrombo-cythemia or chronic myeloid leukemia have been reported to be deficient for platelet lipoxygenase activity (NEJM 1982; 306:381). These patients paradoxically tended to have a greater hemorrhagic tendency rather than thrombotic episodes. We investigated platelet lipoxygenase activity in clearly defined patients with erythromelalgic, thrombotic thrombocythemia (til) (Ann IntMed 1985; 102:466) while on treatment with low dose aspirin in order to prevent platelet activation in vivo or in vitro. The production of hydroxyheptodecatrienoic acid (HHT) by cyclo-oxygenase and 12-hydroxy-eicosatetraenoic acid (12-HETE) by lipoxygenase in 14C labeled platelets after stimulation with thrombin or arachidonic acid were estimated in 12 ETT patients and in 3 patients with reactive thrombocytosis (RT). HHT and 12-HETE were measured with the technique of High Performance Liquid Chromatography. Platelet lipoxygenase activity was completely normal in the 3 patients with RT and in 9 of 12 patients with ETT. Three ETT patients were severely deficient for platelet lipoxygenase activity. Two of them had progressive myeloproliferative disease with very high platelet counts, many large and some giant platelets, a few megakaryoblasts and chromosomal abnormalities of bone marrow cells (trisomy of chromosome 9 and 18p+, 1P-, 11a- respectively). Normal bone marrow karyograms were found in the 9 ETT patients with normal platelet lipoxygenase activity and stable disease. In conclusion platelet lipoxygenase deficiency is not a feature of ETT, but may reflect abnormal megakaryopoesis in progressive myeolo-proliferative disorders.

Download Full-text

Laboratory characteristics of patients with variant Phiadelphia chromosome positive leukemia

10.21203/rs.3.rs-20337/v1 ◽

2020 ◽

Author(s):

Qiling Song ◽

Yangliu Guo ◽

Dongsheng Wang ◽

Qingsong Liu

Keyword(s):

Flow Cytometry ◽

Effective Treatment ◽

Myeloid Leukemia ◽

Bone Marrow Cells ◽

Karyotype Analysis ◽

Chromosome 9 ◽

Flow Cytometry Analysis ◽

Bone Morphology ◽

Leukemia Patient ◽

The Difference

Abstract Background Variant Philadelphia chromosomes are characterized by the involvement of another chromosome in addition to chromosome 9 or 22. To detect the difference between variant Philadelphia chromosomes positive leukemia and classic Philadelphia chromosomes positive leukemia. And to help diagnose and treat variant Philadelphia chromosomes positive leukemia. Methods In this study, Peripheral blood and bone morrow cell morphology test was used to analysis bone morphology of variant Ph positive patients. Karyotype analysis was used to find out variant Ph chromosomes. Flow cytometry analysis was used for immunology analysis. BCR/ABL was detected by PCR to monitor change of molecular genetics in variant Ph positive patients. Results From 48 patients with Ph positive leukemia, we found out 3 variant Ph positive leukemia. Compared with the classic Ph positive leukemia patients, the hemogram in the variant Ph positive leukemia patients was more variant for presenting hypomyelodysplasia or hyperactive. Compared with classic chronic myeloid leukemia which neutrophilic myelocyte, metamyelocyte and stab granulocyte is increasing in, both the morphological testing of bone marrow cells smear and flow cytometry analysis were indicated that proportion of myeloblast and promyelocyte increased in variant Philadelphia chromosomes leukemia. What’s more, the variant Ph with breakpoint 4q31 was the first report in leukemia patient. Same as the classic Ph positive leukemia patient, formal and effective treatment could prolong the survival of patients with variant Ph positive leukemia. Conclusions Compared with classic Ph positive leukemia, the hemogram was more variant in variant Ph. The myeloid morphology in the patients with variant Ph was more immature than that of in the patients with classic Ph. Reporting new cases of complex variant translocations, which can refer to new breakpoints that can eventually be recurrent and important for the understanding of this leukemia. Formal and effective treatment are necessary for variant Ph positve leukemia.

Download Full-text

The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek-can mRNA

Molecular and Cellular Biology ◽

10.1128/mcb.12.4.1687-1697.1992 ◽

1992 ◽

Vol 12 (4) ◽

pp. 1687-1697 ◽

Cited By ~ 1

Author(s):

M von Lindern ◽

M Fornerod ◽

S van Baal ◽

M Jaegle ◽

T de Wit ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Bone Marrow Cells ◽

Fusion Gene ◽

Open Reading Frames ◽

Chromosome 9 ◽

Chromosome 6 ◽

Large Gene ◽

Molecular Masses ◽

Acute Myeloid

The translocation (6;9) is associated with a specific subtype of acute myeloid leukemia (AML). Previously, it was found that breakpoints on chromosome 9 are clustered in one of the introns of a large gene named Cain (can). cDNA probes derived from the 3' part of can detect an aberrant, leukemia-specific 5.5-kb transcript in bone marrow cells from t(6;9) AML patients. cDNA cloning of this mRNA revealed that it is a fusion of sequences encoded on chromosome 6 and 3' can. A novel gene on chromosome 6 which was named dek was isolated. In dek the t(6;9) breakpoints also occur in one intron. As a result the dek-can fusion gene, present in t(6;9) AML, encodes an invariable dek-can transcript. Sequence analysis of the dek-can cDNA showed that dek and can are merged without disruption of the original open reading frames and therefore the fusion mRNA encodes a chimeric DEK-CAN protein of 165 kDa. The predicted DEK and CAN proteins have molecular masses of 43 and 220 kDa, respectively. Sequence comparison with the EMBL data base failed to show consistent homology with any known protein sequences.

Download Full-text

The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek-can mRNA.

Molecular and Cellular Biology ◽

10.1128/mcb.12.4.1687 ◽

1992 ◽

Vol 12 (4) ◽

pp. 1687-1697 ◽

Cited By ~ 250

Author(s):

M von Lindern ◽

M Fornerod ◽

S van Baal ◽

M Jaegle ◽

T de Wit ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Bone Marrow Cells ◽

Fusion Gene ◽

Open Reading Frames ◽

Chromosome 9 ◽

Chromosome 6 ◽

Large Gene ◽

Molecular Masses ◽

Acute Myeloid

Download Full-text

THE CASE VARIANT TRANSLOCATION T(3;9;22)(P24;Q34;Q11) IN CHRONIC MYELOID LEUKEMIA

Problems in oncology ◽

10.37469/0507-3758-2018-64-6-810-814 ◽

2018 ◽

Vol 64 (6) ◽

pp. 810-814

Author(s):

Kodirzhon Boboev ◽

Yuliana Assesorova ◽

Kh. Karimov ◽

B. Allanazarova

Keyword(s):

Adverse Effect ◽

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Fusion Gene ◽

Genetic Locus ◽

Philadelphia Chromosome ◽

Chromosome 9 ◽

Banding Technique ◽

Variant Translocation

This paper presents a case of chronic myeloid leukemia with an earlier unknown variant translocation t (3; 9; 22) (p24; q34; q11) detected by cytogenetic research using the GTG-banding technique. Despite the absence of the classical Philadelphia chromosome, the presence of chromosome 9 and 22 derivatives, as well as the BCR-ABL fusion gene, allow this translocation to be considered pathogenetic for CML. A good response of the patient to the treatment with glivec is that there is no adverse effect on the pathogenesis of the disease of an additional genetic locus (3p24) involved in complex restructuring.

Download Full-text

A review of current knowledge of myeloproliferative disorders in the horse

Acta Veterinaria Scandinavica ◽

10.1186/s13028-021-00573-3 ◽

2021 ◽

Vol 63 (1) ◽

Author(s):

Katy Satué ◽

Juan Carlos Gardon ◽

Ana Muñoz

Keyword(s):

Bone Marrow ◽

Myeloid Leukemia ◽

Current Knowledge ◽

Myeloproliferative Neoplasms ◽

Myeloproliferative Disorders ◽

World Health ◽

Chronic Granulocytic Leukemia ◽

Current State ◽

Multiple Cell ◽

Health Organization

AbstractMyeloid disorders are conditions being characterized by abnormal proliferation and development of myeloid lineage including granulocytes (neutrophils, eosinophils and basophils), monocytes, erythroids, and megakaryocytes precursor cells. Myeloid leukemia, based on clinical presentation and proliferative rate of neoplastic cells, is divided into acute (AML) and myeloproliferative neoplasms (MPN). The most commonly myeloid leukemia reported in horses are AML-M4 (myelomonocytic) and AML-M5 (monocytic). Isolated cases of AML-M6B (acute erythroid leukemia), and chronic granulocytic leukemia have also been reported. Additionally, bone marrow disorders with dysplastic alterations and ineffective hematopoiesis affecting single or multiple cell lineages or myelodysplastic diseases (MDS), have also been reported in horses. MDSs have increased myeloblasts numbers in blood or bone marrow, although less than 20%, which is the minimum level required for diagnosis of AML. This review performed a detailed description of the current state of knowlegde of the myeloproliferative disorders in horses following the criteria established by the World Health Organization.

Download Full-text

Erythropoietin-dependent transformation of myelodysplastic syndrome to acute monoblastic leukemia

Blood ◽

10.1182/blood.v98.12.3492 ◽

2001 ◽

Vol 98 (12) ◽

pp. 3492-3494 ◽

Cited By ~ 29

Author(s):

Udomsak Bunworasate ◽

Hilal Arnouk ◽

Hans Minderman ◽

Kieran L. O'Loughlin ◽

Sheila N. J. Sait ◽

...

Keyword(s):

Myelodysplastic Syndrome ◽

Bone Marrow Cells ◽

Tritiated Thymidine ◽

Flow Cytometric Analysis ◽

Refractory Anemia ◽

Laboratory Findings ◽

Flow Cytometric ◽

Acute Monoblastic Leukemia ◽

Leukemia Cutis ◽

Marrow Cells

Abstract Acute monoblastic leukemia (acute myeloid leukemia [AML], French-American-British type M5a) with leukemia cutis developed in a patient 6 weeks after the initiation of erythropoietin (EPO) therapy for refractory anemia with ringed sideroblasts. AML disappeared from both marrow and skin after the discontinuation of EPO. Multiparameter flow cytometric analysis of bone marrow cells demonstrated coexpression of the EPO receptor with CD45 and CD13 on the surface of blasts. The incubation of marrow cells with EPO, compared to without, resulted in 1.3- and 1.6-fold increases, respectively, in tritiated thymidine incorporation and bromodeoxyuridine incorporation into CD13+ cells. Clinical and laboratory findings were consistent with the EPO-dependent transformation of myelodysplastic syndrome (MDS) to AML. It is concluded that leukemic transformation in patients with MDS treated with EPO may be EPO-dependent and that management should consist of the discontinuation of EPO followed by observation, if clinically feasible.

Download Full-text