Open AccessJournal Article
Southern Blot Analysis of ALL-1 Rearrangements at Chromosome 11q23 in Acute Leukemia
Francesco Lo Coco,Franco Mandelli,Massimo Breccia,Luciana Annino,Cesare Guglielmi,Maria Concetta Petti,Anna Maria Testi,Giuliana Alimena,Carlo M. Croce,Eli Canaani,Giuseppe Cimino +10 more
TLDR
It is concluded that ALL-1 rearrangements are new molecular markers of human leukemia with considerable diagnostic and prognostic relevance.Abstract:
The chromosome 11q23 band is a genetic region frequently involved in nonrandom karyotypic abnormalities of acute leukemia. A genomic locus named ALL-1 or MLL, where 11q23 breakpoints are clustered, has been recently cloned and characterized. We have made use of an ALL-1-specific probe in Southern blot experiments to analyze the configuration of this gene in a large series of acute leukemia patients, representative of all different myeloid and lymphoid subtypes. Nine of 145 cases (6.2%) showed abnormal ALL-1 restriction fragments in leukemic DNAs. Of these nine cases, five patients in whom karyotypic data were available displayed chromosome 11q23 aberrations, including t(4;11) (three cases) and t(9;11) (two cases). Immunophenotypic and morphocytochemical characterization of ALL-1-rearranged acute leukemia revealed prevalence of poorly differentiated B lymphoid and/or monoblastic features. Considering the whole series, ALL-1 rearrangements were significantly associated with female sex, higher white blood cell counts at presentation, and very poor clinical outcome. The presence of residual disease was molecularly documented in one case at the time of clinical remission after induction treatment and was followed by early relapse. We conclude that ALL-1 rearrangements are new molecular markers of human leukemia with considerable diagnostic and prognostic relevance.read more
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An Mll–AF9 Fusion Gene Made by Homologous Recombination Causes Acute Leukemia in Chimeric Mice: A Method to Create Fusion Oncogenes
Javier Corral,Isabelle Lavenir,Helen Impey,Alan J. Warren,Alan Forster,Teresa A Larson,Sarah Bell,Andrew N. J. McKenzie,Gareth King,Terence H. Rabbitts +9 more
TL;DR: This novel use of homologous recombination formally proves that chromosomal translocations contribute to malignancy and provides a general strategy to create fusion oncogenes for studying their role in tumorigenesis.
Journal ArticleDOI
MLL and CALM Are Fused to AF10 in Morphologically Distinct Subsets of Acute Leukemia With Translocation t(10;11): Both Rearrangements Are Associated With a Poor Prognosis
Martin Dreyling,K. Schrader,C. Fonatsch,Brigitte Schlegelberger,Detlef Haase,Claudia Schoch,W.-D. Ludwig,H. Löffler,T. Büchner,Bernhard Wörmann,Wolfgang Hiddemann,Stefan K. Bohlander +11 more
TL;DR: It is concluded that the t(10;11)(p13;q14) indicates CALM and MLL rearrangements in morphologically distinct subsets of acute leukemia and may be associated with a poor prognosis.
Journal ArticleDOI
Gene Expression Profiling of Acute Myeloid Leukemia with Translocation t(8;16)(p11;p13) and MYST3-CREBBP Rearrangement Reveals a Distinctive Signature with a Specific Pattern of HOX Gene Expression
Mireia Camós,Jordi Esteve,Pedro Jares,Dolors Colomer,María Rozman,Neus Villamor,Dolors Costa,Ana Carrió,Josep F. Nomdedeu,Emili Montserrat,Elias Campo +10 more
TL;DR: This study shows the distinctive gene expression profile of MYST3-CREBBP AML, with overexpression of RET and PRL and a specific pattern of HOX gene expression.
Journal ArticleDOI
Acute myeloid leukemia with MLL rearrangements: clinicobiological features, prognostic impact and value of flow cytometry in the detection of residual leukemic cells
Luz Muñoz,Josep F. Nomdedeu,Neus Villamor,Ramon Guardia,Dolors Colomer,Josep-Maria Ribera,JP Torres,Juan Berlanga,C. Fernández,Andreu Llorente,Queipo de Llano Mp,José María Raya Sánchez,Salut Brunet,Jordi Sierra +13 more
TL;DR: In conclusion, immunophenotyping may be a suitable approach to investigating MRD status in AML patients with PTD of the MLL gene.
Journal ArticleDOI
Clinical and biological implications of partial tandem duplication of the MLL gene in acute myeloid leukemia without chromosomal abnormalities at 11q23.
Shiah Hs,Yuan-Yeh Kuo,Jih-Luh Tang,Shang-Yi Huang,Ming Yao,Woei Tsay,Chen Yc,Wang Ch,Ming-Ching Shen,Lin Dt,Kai-Hsin Lin,Hwei-Fang Tien +11 more
TL;DR: Partial tandem duplication of the MLL gene is associated with increased expression of CD11b on leukemic blasts and implicates poor prognosis in adult AML patients and the higher frequency of MLL duplication in children older than 1 year, than in other age groups, needs to be confirmed by further studies.
References
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Journal ArticleDOI
An analysis of leukemic cell chromosomal features in infants.
Ching-Hon Pui,Susana C. Raimondi,Sharon B. Murphy,Raul C. Ribeiro,David K. Kalwinsky,Gary V. Dahl,William M. Crist,Dorothy L. Williams +7 more
TL;DR: The CALLA- or pre-B phenotype and the presence of chromosomal translocations in most infants with ALL provide a biological explanation for their poor prognosis.
Journal ArticleDOI
ALL-1 gene at chromosome 11q23 is consistently altered in acute leukemia of early infancy
Giuseppe Cimino,F Lo Coco,A Biondi,Loredana Elia,A Luciano,CM Croce,G Masera,Franco Mandelli,E Canaani +8 more
TL;DR: Analysis of the ALL-1 genomic configuration in DNA from 15 infants with AL showed specific ALL- 1 rearrangements in 12 cases (80%), including 5 with normal karyotypes, which indicates that a consistent genetic defect underlies this particular leukemic subset.
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Impact of chromosomal translocations on prognosis in childhood acute lymphoblastic leukemia.
Charles M. Rubin,M M Le Beau,Rosemarie Mick,Mitchell A. Bitter,James B. Nachman,R Rudinsky,H J Appel,Elaine R. Morgan,Carlos R. Suarez,H R Schumacher +9 more
TL;DR: Categorization of patients on the basis of chromosomal translocations without attention to the specific abnormality is not useful as a prognostic factor when effective intensive therapy is used to treat childhood ALL with high-risk clinical features.
Journal ArticleDOI
A 2p;11q chromosome translocation in dysmyelopoietic preleukemia.
TL;DR: Three patients with dysmyelopoietic preleukemia had a marrow clone with translocation t(2;11)(p21;q23) as the only chromosome change, and in one patient, the cytogenetically altered cells disappeared following treatment with 13-cis-retinoic acid.
Journal ArticleDOI
Translocation t(1;11)(q21;q23), a new subgroup within M4 acute nonlymphocytic leukemia.
TL;DR: A case of acute myelomonocytic leukemia (M4) with a t(1;11)(q21;q23) as the sole chromosome anomaly is presented and the results point to the possibility of a subgroup within M4.