Tracing the development of acute myeloid leukemia in CBL syndrome.
We describe the development of acute myeloid leukemia (AML) in an adult with CBL syndrome caused by a heterozygous de novo germline mutation in CBL codon D390. In the AML bone marrow, the mutated CBL allele was homozygous after copy number-neutral loss-of-heterozygosity and amplified through a chromosomal gain; moreover, an inv(16)(p13q22) and, as assessed by whole-exome sequencing, 12 gene mutations (eg, in CAND1, NID2, PTPRT, DOCK6) were additionally acquired. During complete remission of the AML, in the presence of normal blood counts, the hematopoiesis stably maintained the homozygous CBL mutation, which is reminiscent of the situation in children with CBL syndrome and transient juvenile myelomonocytic leukemia. No additional mutations were identified by whole-exome sequencing in granulocytes during complete remission. The study highlights the development of AML in an adult with CBL syndrome and, more generally, in genetically aberrant but clinically inconspicuous hematopoiesis.
Department of Medicine I, Medical Center-University of Freiburg, Freiburg, Germany;
Heiko
H
Becker
Kenichi
K
Yoshida
Nadja
N
Blagitko-Dorfs
Rainer
R
Claus
Milena
M
Pantic
Mahmoud
M
Abdelkarim
Christoph
C
Niemöller
Christine
C
Greil
Björn
B
Hackanson
Yuichi
Y
Shiraishi
Kenichi
K
Chiba
Hiroko
H
Tanaka
Satoru
S
Miyano
Konstanze
K
Döhner
Susanne
S
Schnittger
Philipp
P
Henneke
Charlotte M
CM
Niemeyer
Christian
C
Flotho
Dietmar
D
Pfeifer
Seishi
S
Ogawa
Michael
M
Lübbert
D000328:Adult; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D005784:Gene Amplification; D018095:Germ-Line Mutation; D006402:Hematologic Diseases / Q000150:complications / Q000235:genetics; D006410:Hematopoiesis / Q000235:genetics; D006720:Homozygote; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics*; D013103:Spherocytosis, Hereditary / Q000150:complications / Q000235:genetics; D013577:Syndrome
D050721:Proto-Oncogene Proteins c-cbl; C067419:CBL protein, human