Clinical and molecular characterization of a rare syndrome of acute promyelocytic leukemia associated with translocation (11;17).
Analysis of a variant translocation t(11;17) in a case of acute promyelocytic leukemia (APL) led to discovery of a novel zinc finger gene, PLZF, fused to the retinoic acid receptor-alpha (RAR alpha) gene. We reviewed the clinical and molecular features of five additional patients with t(11;17)-associated APL. The clinical course of three patients was characterized by early death and three experienced disseminated intravascular coagulation. Morphologically all of the patients fell in a unusual morphologic spectrum of APL, with features intermediate between M2 and M3 AML. All six patients had PLZF-RAR alpha gene fusion as detected by reverse transcription/polymerase chain reaction assay, Southern blotting, or pulsed-field gel electrophoresis. Five of the six patients failed to achieve complete remission after initial chemotherapy or differentiation therapy with all-trans retinoic acid (ATRA). A sixth patient responded to initial chemotherapy, but on relapse failed to respond to ATRA. When tested in vitro, cultured cells from three of the patients failed to differentiate in response to ATRA. APL associated with t(11;17) and fusion of the PLZF and RAR alpha genes is a discrete clinico-pathologic syndrome with a distinctly worse prognosis than t(15;17) APL.
Division of Molecular Medicine, Mount Sinai Medical Center, New York, NY 10029.
J D
JD
Licht
C
C
Chomienne
A
A
Goy
A
A
Chen
A A
AA
Scott
D R
DR
Head
J L
JL
Michaux
Y
Y
Wu
A
A
DeBlasio
W H
WH
Miller
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001483:Base Sequence; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D003001:Cloning, Molecular; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D015473:Leukemia, Promyelocytic, Acute / Q000145:classification / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D018168:Receptors, Retinoic Acid / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic; D014212:Tretinoin / Q000627:therapeutic use; D016335:Zinc Fingers / Q000235:genetics
D017931:DNA Primers; D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C000607071:RARA protein, human; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; C092037:ZBTB16 protein, human; D014212:Tretinoin