Chronic lymphocytic leukemia and prolymphocytic leukemia with MYC translocations: a subgroup with an aggressive disease course.
Translocations involving MYC are rare in chronic lymphocytic leukemia (CLL), and up to now, their prognostic significance remains unclear. We report the characteristics of 21 patients with CLL and nine patients with prolymphocytic leukemia (PLL), diagnosed in multiple centers (n = 13), which showed an MYC translocation demonstrated by fluorescence in situ hybridization. The prevalence was estimated to be <1%. Advanced age and male predominance were observed. Morphological analysis frequently revealed the presence of prolymphocytes. A typical "CLL-immunophenotype" was found in four of nine cases with PLL. Moreover, CD5 and CD23 were frequently expressed in PLL. The latter findings are atypical for PLL and may suggest transformation or progression of an underlying CLL. MYC translocations were frequently observed with concomitant adverse cytogenetic markers, such as del(11q) (n = 8/30) and/or del(17p)/monosomy 17 (n = 7/30). In addition, the presence of unbalanced translocations (n = 24 in 13/30 cases) and complex karyotype (n = 16/30) were frequent in cases with MYC translocations. Altogether, del(17p)/monosomy 17, del(11q), and/or complex karyotype were observed in 22 of 30 patients. Survival outcome was poor: the median time to treatment was only 5 months, and overall survival (OS) from clinical diagnosis and from genetic detection was 71 and 19 months, respectively. In conclusion, CLL/PLL with MYC translocations is a rare entity, which seems to be associated with adverse prognostic features and unfavorable outcome.
Center for Human Genetics, Catholic University of Leuven, Belgium.
Natalie
N
Put
Katrien
K
Van Roosbroeck
Peter
P
Konings
Peter
P
Meeus
Caroline
C
Brusselmans
Katrina
K
Rack
Carine
C
Gervais
Florence
F
Nguyen-Khac
Elise
E
Chapiro
Isabelle
I
Radford-Weiss
Stéphanie
S
Struski
Nicole
N
Dastugue
Nathalie
N
Gachard
Christine
C
Lefebvre
Carole
C
Barin
Virginie
V
Eclache
Sandra
S
Fert-Ferrer
Sophy
S
Laibe
Marie-Joëlle
MJ
Mozziconacci
Benoît
B
Quilichini
Hélène A
HA
Poirel
Iwona
I
Wlodarska
Anne
A
Hagemeijer
Yves
Y
Moreau
Peter
P
Vandenberghe
Lucienne
L
Michaux
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D015463:Leukemia, Prolymphocytic / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012189:Retrospective Studies; D014178:Translocation, Genetic