Two acute monocytic leukemia (AML-M5a) cell lines (MOLM-13 and MOLM-14) with interclonal phenotypic heterogeneity showing MLL-AF9 fusion resulting from an occult chromosome insertion, ins(11;9)(q23;p22p23)

• Published in: Leukemia Vol. 11; no. 9; pp. 1469 - 1477
• Main Authors: MATSUO, Y, MACLEOD, R. A. F, ORITA, K, UPHOFF, C. C, DREXLER, H. G, NISHIZAKI, C, KATAYAMA, Y, KIMURA, G, FUJII, N, OMOTO, E, HARADA, M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.09.1997; Nature Publishing Group
• Subjects: Acute monocytic leukemia; Acute myeloid leukemia; Adult; Antigens; Antigens, CD - metabolism; Biological and medical sciences; CD13 antigen; CD14 antigen; CD34 antigen; CD4 antigen; Chromosome Aberrations - genetics; Chromosome Banding; Chromosome Disorders; Chromosome rearrangements; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 9; Cytokines - pharmacology; Cytology; Differentiation; DNA, Neoplasm - genetics; DNA-Binding Proteins - genetics; Esterase; Gene Expression Regulation, Neoplastic; Gene fusion; Gene rearrangement; Hematologic and hematopoietic diseases; Heterogeneity; Histone-Lysine N-Methyltransferase; Humans; Immunophenotyping; In Situ Hybridization, Fluorescence; Insertion; Karyotyping; Leukemia; Leukemia, Monocytic, Acute - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukemogenesis; Macrophages; Male; Medical sciences; MLL protein; Monocytes; Monocytic leukemia; mRNA; Myelodysplastic syndrome; Myelodysplastic syndromes; Myeloid-Lymphoid Leukemia Protein; Nuclear Proteins - genetics; Peripheral blood; Phenotype; Proto-Oncogenes; RNA, Messenger - genetics; Transcription Factors; Trisomy; Tumor cell lines; Tumor Cells, Cultured; Tumor necrosis factor-α; Chromosomal aberration; Human; Monoblastic leukemia; Chromosome insertion; Acute; Malignant hemopathy; Case study; Abnormal chromosome C9; Heterogeneity; Phenotype; Young adult; Established cell line; Cytogenetics; Abnormal chromosome; Abnormal chromosome C11; Hybrid gene; Chromosome translocation
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2400768

We describe two new human leukemia cell lines, MOLM-13 and MOLM-14, established from the peripheral blood of a patient at relapse of acute monocytic leukemia, FAB M5a, which had evolved from myelodysplastic syndrome (MDS). Both cell lines express monocyte-specific esterase (MSE) and MLL-AF9 fusion mRNA. Gene fusion is associated with a minute chromosomal insertion, ins(11;9)(q23;p22p23). MOLM-13 and MOLM-14 are the first cell lines with, and represent the third reported case of, MLL gene rearrangement arising via chromosomal insertion. Both cell lines carry trisomy 8 which was also present during the MDS phase, as well as the most frequent trisomies associated with t(9;11), ie, +6, +13, +19 variously present in different subclones. Despite having these features in common, differences in antigen expression were noted between the two cell lines: that of MOLM-13 being CD34+, CD13-, CD14-, CD15+, CD33+; whereas MOLM-14 was CD4+, CD13+, CD14+, CD15+, CD33+. Differentiation to macrophage-like morphology could be induced in both cell lines after stimulation with INF-gamma alone, or in combination with TNF-alpha, which treatment also induced or upregulated, expression of certain myelomonocyte-associated antigens, including CD13, CD14, CD15, CD64, CD65 and CD87. Together, these data confirm that both cell lines are likely to be novel in vitro models for studying monocytic differentiation and leukemogenesis.