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

Some anaplastic large cell lymphomas (ALCLs) carry a specific chromosomal translocation, t(2;5)(p23;q35). Recently, we found a novel hyperphosphorylated 80-kDa protein tyrosine kinase, p80, in ALCLs with t(2;5). Subsequent cDNA cloning revealed p80 to be a fusion protein of two genes, the novel tyrosine kinase gene and the nucleophosmin gene, in accordance with the sequence of the NPM/ALK gene (Morris et al.). Meanwhile, the clinicopathologic features of p80-carrying ALCLs have remained unclear. Paraffin sections of 105 cases of ALCL were immunostained using anti-p80 antibody, and 30 of them were shown to express p80. Clinicopathological comparison between p80-positive and -negative ALCLs revealed that p80-positive cases occurred in a far younger patient age group and the patients showed a far better 5-year survival rate. These data showed that p80-positive ALCL is a distinct entity both clinically and pathogenetically, and should be differentiated from p80-negative ALCL.
Leukemia 1997 Apr
PMID:Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: a distinct clinicopathologic entity. 920 50

A wide variety of abnormalities of the short arm of chromosome 12 has been reported in hematologic malignancies. The most frequent rearrangements result from t(12;21)(p13;q22) of childhood acute lymphoblastic leukemia, a translocation cryptic when leukemic cells are analyzed with chromosome banding techniques. This translocation results in a fusion of the TEL/ETV6 and AML1 genes. In this report, examples of rearrangements of 12p are presented. Study of two complex chromosome abnormalities associated with t(12;21) emphasizes the importance of using FISH in detection of such translocations. Three novel translocations involving the TEL/ETV6 gene localized on 12p13 are also reported: t(X;12)(q28;p13), t(1;12)(q21;p13), and t(9;12)(p23-24;p13). Finally, the presentation of two translocations with breakpoints located centromeric to TEL/ETV6 highlights the not uncommon involvement of genes other than TEL/ETV6 on 12p.
Leukemia 1997 Sep
PMID:Chromosome abnormalities of the short arm of chromosome 12 in hematopoietic malignancies: a report including three novel translocations involving the TEL/ETV6 gene. 930 91

The nucleophosmin (NPM) gene is involved in two recurrent translocations in hematological malignancies: t(2;5) (p23;q35) in anaplastic large cell lymphoma (ALCL) and t(3;5)(q25.1;q34-35) in myelodysplasia and acute non-lymphocytic leukemia (ANLL). Using eight YACs encompassing the 5q34-q35 region, we could easily detect these two translocations. In both types of translocation, probable unexpected deletions were also discovered downstream of the breakpoint at 5q35.
Leukemia 1998 Jul
PMID:Non-Hodgkin's lymphomas and myeloid disorders: deletions associated with t(2;5) and t(3;5) detected by FISH. 966 4

A 7-month-old girl was diagnosed with acute megakaryoblastic leukemia and, at the time of diagnosis, the karyotype was 48-50,XX,+4,+5,del(5)(p13),del(6)(q14), +8,inv(8)(p23.1q13),der(13) t(13;?;?),+19,-20,+21,+22,+mar [cp20]. At relapse, there was clear evidence of her constitutional status as a carrier of the pericentric inversion (8)(p23.1q13). It was a familial inversion affecting the patient's maternal lineage; a history of cancer and bleeding anomalies in carriers of the inversion led us to consider their nonrandom association with these pathologies.
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PMID:Acute megakaryoblastic leukemia in a patient with a familial pericentric inversion of chromosome 8, inv(8)(p23.1q13). 968 34

Translocation t(6:9)(p23;q34), resulting in a dek-can gene fusion, is a recurrent chromosomal abnormality mainly associated with specific subtypes of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). Patients with this type of chromosomal change are usually young and their prognosis is poor. The role of fusion protein generated from dek-can chimaeric transcript on the leukaemogenesis oft(6;9) AML or MDS is as yet unknown. We have established the first permanent cell line (FKH-1) with t(6;9). derived from the peripheral blood of a patient with t(6:9) AML transformed from Philadelphia chromosome (Ph1)-negative chronic myelocytic leukaemia (CML). The FKH-1 expressed myelomonocytic markers and dek-can chimaeric transcript. In the presence of 10 ng/ml recombinant human granulocyte colony-stimulating factor (G-CSF), the cells doubled every 54 h and showed multilineage myeloid differentiation, resulting in heterogenous morphologies such as macrophages, basophils, eosinophils and neutrophils. Thus, this cell line may be derived from a pluripotent myeloid stem cell and should be a useful tool for biomolecular studies on the pathogenesis of t(6;9) myeloid malignancies which have rarely been investigated because of the lack of continuously proliferating cells.
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PMID:Establishment of a novel human myeloid leukaemia cell line (FKH-1) with t(6;9)(p23;q34) and the expression of dek-can chimaeric transcript. 975 53

Chromosomal translocations are frequently linked to multiple hematological malignancies. The study of the resulting abnormal gene products has led to fundamental advances in the understanding of cancer biology. This is the first report of t(2;15)(p23;q22) and t(2;17)(p23;q21) translocations in human malignancy. Patient 1, a 73-year-old male, was diagnosed with myeloblastic (FAB M1 sub-type) AML. Cytogenetic analysis showed a 47,XY,t(2;15)(p23;q22),+13 karyotype. Fluorescent in situ hybridization (FISH) showed that the PML gene was transferred intact to the short arm of chromosome 2 while the ALK gene on chromosome 2p23 was passively transferred to the long arm of chromosome 15. Patient 2 was a 60-year-old male diagnosed with monocytic (FAB M4-type) AML. Cytogenetic analysis showed 46,XY,t(2;17)(p23;q21) karyotype. FISH analysis showed that neither RARalpha nor ALK were disrupted by the translocation. None of the coding region of the three genes studied were translocated in these patients. This raises the possibilities that other neighboring genes could be involved or that noncoding regulatory sequences of the studied genes could be put in contact and deregulate expression of other genes. Alternatively, displacement of ALK, RARalpha and PML to novel positions could lead to loss of their normal regulation
Leukemia 1999 Oct
PMID:Identification of novel chromosomal rearrangements in acute myelogenous leukemia involving loci on chromosome 2p23, 15q22 and 17q21. 1051 54

We report a unique case of de novo acute promyelocytic leukemia (APL) with cryptic 15;17 rearrangements. Cytogenetically, structural rearrangements of the 6p23 region has been reported mainly in secondary leukemia. This patient had a karyotype of 46, XY, del(6)(p23) and no additional chromosomal abnormalities. Molecular analyses revealed the presence of PML-RAR alpha fusion genes. Deletion of the 6p23 region is extremely rare in APL.
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PMID:Acute promyelocytic leukemia with del(6)(p23). 1063 50

Despite its clinical and histological heterogeneity, anaplastic large cell lymphoma (ALCL) is now a well-recognized clinicopathological entity accounting for 2% of all adult non-Hodgkin's lymphomas (NHL) and about 13% of pediatric NHL. Immunophenotypically, ALCL are of T cell (predominantly) or Null cell type; by definition, cases expressing B cell antigens are officially not included in this entity. The translocation (2;5)(p23;q35) is a recurring abnormality in ALCL; 46% of the ALCL patients bear this signature translocation. This translocation creates a fusion gene composed of nucleophosmin (NPM) and a novel receptor tyrosine kinase gene, named anaplastic lymphoma kinase (ALK). The NPM-ALK chimeric gene encodes a constitutively activated tyrosine kinase that has been shown to be a potent oncogene. The exact pathogenetic mechanisms leading to lymphomagenesis remain elusive; however, the synopsis of evidence obtained to date provides an outline of likely scenarios. Several t(2;5) variants have been described; in some instances, the breakpoints have been cloned and the genes forming a new fusion gene with ALK have been identified: ATIC-ALK, TFG-ALK and TPM3-ALK. Cloning the translocation breakpoint and identifying the ALK and NPM genes provided tools for screening material from patients with ALCL using various approaches at the chromosome, DNA, RNA, or protein level: positive signals in the reverse transcriptase-polymerase chain reaction (RT-PCR) and the immunostaining with anti-ALK monoclonal antibodies (McAb) serve as the most convenient tests for detection of the t(2;5) NPM-ALK since the fusion gene and ALK protein expression do not occur in normal or reactive lymphoid tissue. The wide range of NPM-ALK positivity reported in different series appears to be dependent on the inclusion and selection criteria of the ALCL cases studied. Overall, however, 43% of ALCL cases were NPM-ALK+ (83% of pediatric ALCL vs 31% of adult ALCL). Occasional non-ALCL B cell lymphomas (4%) with diffuse large cell and immunoblastic histology and Hodgkin's disease cases (3%) were NPM-ALK-, but these data are questionable. The aggregate results indicate that, in contrast to primary nodal (systemic) ALCL, the t(2;5) may be present in only 10-20% of primary cutaneous ALCL and rarely, if at all, in lymphomatoid papulosis, a potential precursor lesion; however, these 10-20% positive cases were not confirmed by anti-ALK McAb immunostaining and may represent an overestimate. Positivity for NPM-ALK is associated to various degrees with the following parameters: 44% and 45% of ALCL cases with T cell and Null cell immunophenotype, respectively, are positive, whereas only 8% of cases with a B cell immunoprofile are positive; the mean age of positive patients is significantly younger than that of negative patients; positive cases carry a better overall prognosis (but not in all studies). Recently, the homogenous category of ALK lymphoma ('ALKoma') has emerged as a distinct pathological entity within the heterogenous group of ALCL. The fact that patients with ALK lymphomas experience significantly better overall survival than ALK- ALCL demonstrates further that analysis of ALK expression has important prognostic implications. The term ALK lymphoma signifies a switch in the use of the diagnostic criteria: cases are selected on the basis of a genetic abnormality (the ALK rearrangement), instead of the review of morphological or immunophenotypical features which are clearly more prone to disagreement and controversy. Since its initial description in 1985 ALCL has become one of the best characterized lymphoma entities.
Leukemia 2000 Sep
PMID:Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas. 1099 99

This report describes an unusual extramedullary hematologic malignancy in an 18-month-old child who presented with a capillary leak syndrome that evolved into hyperleukocytosis with malignant cells. The circulating tumor cells did not express an antigen profile typical of any subtype of leukemia commonly observed in children. Tumor cells were CD3(-)/CD56(+); had germline TCR genes; and strongly expressed CD30, epithelial membrane antigen, and anaplastic lymphoma kinase (ALK) consistent with a null cell anaplastic large cell lymphoma (ALCL). The malignant cells contained a t(2;19)(p23;p13.1) that interrupted ALK and translocated it to the der(19). Reverse transcriptase-polymerase chain reaction and nucleotide sequence analysis revealed fusion of ALK to tropomyosin 4, an ALK fusion partner not described previously in hematologic malignancies. The clinical presentation and phenotypic features of this malignancy were not typical for ALCL because tumor cells expressed both myeloid (CD13, CD33, HLA-DR) and natural killer (NK) cell antigens. The neoplastic cells most resembled NK cells because in addition to being CD3(-)/CD56(+) with germline TCR genes, these cells were CD25(+)/CD122(+)/granzyme B(+) and possessed the functional properties of immature NK cells. The unusual clinical presentation, immunophenotype, and functional properties of these neoplastic cells suggest that this malignancy may be derived from the putative myeloid-NK precursor cell. Furthermore co-expression of NK and ALCL features supports the concept that a minority of null-ALCL may be derived from NK cells and expands the spectrum of phenotypes that can be seen in tumors produced by ALK fusion proteins. (Blood. 2001;98:1209-1216)
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PMID:Unusual childhood extramedullary hematologic malignancy with natural killer cell properties that contains tropomyosin 4--anaplastic lymphoma kinase gene fusion. 1149 72

Acute basophilic leukemia has recently been included into a revised classification of acute leukemias proposed by the WHO panel. Due to the rarity of the disease, consistent diagnostic criteria are lacking. We report on two cases of acute basophilic leukemia that occurred in our department during the last 10 yr. We focus on their clinical, morphological and cytogenetic presentation. Both patients were >60 yr of age, and presented in good clinical condition with alterations to their full blood count. None had cutaneous symptoms such as erythema or urticaria. Cytogenetic analyses in the first patient showed a normal karyotype, while the second displayed a translocation t(2;6); (q23?4;p22?3), as well as a del (12)(p11). Earlier observations have linked bone marrow basophilia either to a deletion of the short arm of chromosome 12 (p11-13), to translocations involving the long arm of chomosome 6 at 6q23 or to the translocation t(6,9); (p23;q34). However, other translocations involving chromosome 6p23 have not been described before. Treatment of our patients consisted of supportive treatment in the one with normal karyotype and aggressive chemotherapy in the other patient. Both patients died within one year after diagnosis due to progressive or recurrent leukemia.
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PMID:Acute basophilic leukemia. 1172 93


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