PMID- 10942371
OWN - NLM
STAT- MEDLINE
DCOM- 20000907
LR  - 20220409
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 96
IP  - 4
DP  - 2000 Aug 15
TI  - Characterization of acute promyelocytic leukemia cases lacking the classic 
      t(15;17): results of the European Working Party. Groupe Francais de Cytogenetique 
      Hematologique, Groupe de Francais d'Hematologie Cellulaire, UK Cancer 
      Cytogenetics Group and BIOMED 1 European Community-Concerted Action "Molecular 
      Cytogenetic Diagnosis in Haematological Malignancies".
PG  - 1297-308
AB  - Acute promyelocytic leukemia (APL) is typified by the t(15;17), generating the 
      PML-RAR alpha fusion and predicting a beneficial response to retinoids. However, 
      a sizeable minority of APL cases lack the classic t(15;17), prompting the 
      establishment of the European Working Party to further characterize this group. 
      Such cases were referred to a workshop held in Monza, Italy and subjected to 
      morphologic, cytogenetic, and molecular review, yielding 60 evaluable patients. 
      In the majority (42 of 60), molecular analyses revealed underlying PML/RAR alpha 
      rearrangements due to insertions (28 of 42) or more complex mechanisms, including 
      3-way and simple variant translocations (14 of 42). Metaphase fluorescence in 
      situ hybridization (FISH) demonstrated that insertions most commonly led to 
      formation of the PML-RAR alpha fusion gene on 15q. In 11 of 60 workshop patients, 
      PLZF/RAR alpha rearrangements were identified, including 2 patients lacking the 
      t(11;17)(q23;q21). In one case with a normal karyotype, FISH analysis revealed 
      insertion of RAR alpha into 11q23, and PLZF-RAR alpha was the sole fusion gene 
      formed. Two patients were found to have t(5;17), one with a diffuse nuclear NPM 
      staining pattern and with NPM-RAR alpha and RAR alpha-NPM transcripts detected. 
      In the other with an unbalanced der(5)t(5;17)(q13;q21) and a nucleolar NPM 
      localization pattern, an NPM/RAR alpha rearrangement was excluded, and FISH 
      revealed deletion of one RAR alpha allele. In the remaining 5 workshop patients, 
      no evidence was found for a rearrangement of RAR alpha, indicating that in rare 
      instances, alternative mechanisms could mediate the differentiation block that 
      typifies this disease. This study highlights the importance of combining 
      morphologic, cytogenetic, and molecular analyses for optimal management of APL 
      patients and better understanding of the pathogenesis of the disease. (Blood. 
      2000;96:1297-1308)
FAU - Grimwade, D
AU  - Grimwade D
AD  - Division of Medical and Molecular Genetics, Guy's, King's, and St. Thomas' School 
      of Medicine, London, United Kingdom.
FAU - Biondi, A
AU  - Biondi A
FAU - Mozziconacci, M J
AU  - Mozziconacci MJ
FAU - Hagemeijer, A
AU  - Hagemeijer A
FAU - Berger, R
AU  - Berger R
FAU - Neat, M
AU  - Neat M
FAU - Howe, K
AU  - Howe K
FAU - Dastugue, N
AU  - Dastugue N
FAU - Jansen, J
AU  - Jansen J
FAU - Radford-Weiss, I
AU  - Radford-Weiss I
FAU - Lo Coco, F
AU  - Lo Coco F
FAU - Lessard, M
AU  - Lessard M
FAU - Hernandez, J M
AU  - Hernandez JM
FAU - Delabesse, E
AU  - Delabesse E
FAU - Head, D
AU  - Head D
FAU - Liso, V
AU  - Liso V
FAU - Sainty, D
AU  - Sainty D
FAU - Flandrin, G
AU  - Flandrin G
FAU - Solomon, E
AU  - Solomon E
FAU - Birg, F
AU  - Birg F
FAU - Lafage-Pochitaloff, M
AU  - Lafage-Pochitaloff M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Genetic Markers)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Chromosomes, Human, Pair 15
MH  - Chromosomes, Human, Pair 17
MH  - Female
MH  - *Gene Rearrangement
MH  - *Genetic Markers
MH  - Humans
MH  - Karyotyping
MH  - Leukemia, Promyelocytic, Acute/*diagnosis/*genetics
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Proteins/*genetics
MH  - Oncogene Proteins, Fusion/*genetics
MH  - Translocation, Genetic
EDAT- 2000/08/15 11:00
MHDA- 2000/09/09 11:01
CRDT- 2000/08/15 11:00
PHST- 2000/08/15 11:00 [pubmed]
PHST- 2000/09/09 11:01 [medline]
PHST- 2000/08/15 11:00 [entrez]
AID - S0006-4971(20)71943-9 [pii]
PST - ppublish
SO  - Blood. 2000 Aug 15;96(4):1297-308.