MLL gene amplification in acute myeloid leukemia and myelodysplastic syndromes is associated with characteristic clinicopathological findings and TP53 gene mutation.
MLL gene rearrangements are well-recognized aberrations in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). In contrast, MLL gene amplification in AML/MDS remains poorly characterized. Here, we report a series of 21 patients with myeloid neoplasms associated with MLL gene amplification from 1 institution. This series included 13 men and 8 women, with a median age of 64 years. Eleven patients presented as AML with myelodysplasia-related changes, 6 as therapy-related AML, and 4 as therapy-related MDS. All patients had a highly complex karyotype, including frequent -5/del(5q), -18, and -17/del(17p) abnormalities; 16 patients were hypodiploid. TP53 mutations were detected in all 12 patients tested, and 3 patients showed TP53 mutation before MLL amplification. Morphologically, the leukemic cells frequently showed cytoplasmic vacuoles, bilobed nuclei, and were associated with background dyspoiesis. Immunophenotypically, 15 patients had a myeloid and 4 had myelomonocytic immunophenotype. Laboratory coagulopathies were common; 7 patients developed disseminated intravascular coagulopathy, and 3 died of intracranial bleeding. All patients were refractory to therapy; the median overall survival was 1 month, after MLL gene amplification was detected. We concluded that AML/MDS with MLL gene amplification is likely a subset of therapy-related AML/MDS or AML with myelodysplasia-related changes, associated with distinct clinicopathological features, frequent disseminated intravascular coagulopathy, a highly complex karyotype, TP53 deletion/mutation, and an aggressive clinical course.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: gtang@mdanderson.org.
Guilin
G
Tang
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Courtney
C
DiNardo
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Liping
L
Zhang
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Farhad
F
Ravandi
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Joseph D
JD
Khoury
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yang O
YO
Huh
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Tariq
T
Muzzafar
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
L Jeffrey
LJ
Medeiros
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Sa A
SA
Wang
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Carlos E
CE
Bueso-Ramos
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002877:Chromosomes, Human; D004252:DNA Mutational Analysis; D005260:Female; D005784:Gene Amplification; D020022:Genetic Predisposition to Disease; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D010641:Phenotype; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D017211:Treatment Failure; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
C497422:KMT2A protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase
AML/MDS; Cytogenetics; MLL amplification; Pathologic features; TP53 mutation