Therapy-related acute myeloid leukemia 6 years after clonal detection of inv(11)(q21q23) and MLL gene rearrangement.
Results of recent studies with animal models suggest that expression of MLL fusion proteins promotes acute leukemogenesis. However, the most potent MLL fusion proteins are not sufficient for the development of acute myeloid leukemia (AML). The clinical data on the pathogenesis of this type of leukemia are limited. We analyzed the case of a patient with therapy-related AML with MLL rearrangement. The patient initially developed AML with t(8;21). Although the patient achieved complete remission with chemotherapy, an abnormal karyotype, inv(11)(q21q23), was detected. After 6-year persistence of a clone with the inversion 11 karyotype in the bone marrow, secondary AML developed. Results of fluorescence in situ hybridization analysis combined with magnet-activated cell sorting analysis showed that MLL rearrangement was detected in CD34+ and CD13+ fractions but not in a CD3+ fraction of the bone marrow. There were 2 important clinical findings. One was that MLL rearrangement was not sufficient for the development of leukemia. The other was that MLL rearrangement targets specific lineages.
Takei
Naoko
N
Moriya Daiichi General Hospital, Japan.
Suzukawa
Kazumi
K
Mukai
Harumi Yamamoto
HY
Itoh
Takayoshi
T
Okoshi
Yasushi
Y
Yoda
Yasuhiro
Y
Nagasawa
Toshiro
T
D018952:Antigens, CD34 / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D018826:CD13 Antigens / Q000096:biosynthesis; D007446:Chromosome Inversion / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D018952:Antigens, CD34; D051788:Myeloid-Lymphoid Leukemia Protein; D018826:CD13 Antigens