Details

Autor(en) / Beteiligte

• Tang, Guilin, MD, PhD
• DiNardo, Courtney, MD
• Zhang, Liping, MD
• Ravandi, Farhad, MD
• Khoury, Joseph D., MD
• Huh, Yang O., MD
• Muzzafar, Tariq, MD
• Medeiros, L. Jeffrey, MD
• Wang, Sa A., MD
• Bueso-Ramos, Carlos E., MD

Titel

MLL gene amplification in acute myeloid leukemia and myelodysplastic syndromes is associated with characteristic clinicopathological findings and TP53 gene mutation

Ist Teil von

• Human pathology, 2015-01, Vol.46 (1), p.65-73

Ort / Verlag

United States

Erscheinungsjahr

2015

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• Summary 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.