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)

Abstract

without detectable blast infiltration. At diagnosis of MDS, interface cytogenetic and RT-PCR analyses, respectively, showed trisomy 8 and absence of AF9-MLL rearrangement in Introduction the bone marrow (BM). On readmission with florid leukemia, his peripheral white blood cell count was 13 200/mm 3 , with A subtle, reciprocal translocation exchanging the terminal 56% leukemic blasts. His hemoglobin concentration was short and long arm segments of chromosomes 9 and 11, 15.0 g/dl, and his platelet count was 22 000/mm 3 . The bone respectively t(9;11)(p21-22;q23), is associated with acute marrow aspiration showed 92% leukemic blasts, and the mormyeloid leukemia (AML)-M5, 1 particularly the M5a subtype. 2 phological diagnosis was made as AML-M5a. Cytogenetic Ascertainment may be difficult in suboptimal preparations analysis was interpreted as: 47, XY, +8, t(9;11)(p22;q23). and, despite being regarded as the 'standard' cytogenetic Immunophenotyping analysis of fresh leukemia blasts change in acute monoblastic leukemia, its overall incidence revealed no significant expression of CD antigens associated and pattern of associations remain uncertain. 2 A recent study with the myelo-monocytic lineage. CD34 was 30% positive comparing AML-M1 and -M5 patients, analyzed simuland non-lineage-associated HLA-DR was found to be positive taneously by reverse transcriptase-polymerase chain reaction at 70%; whereas those indicative of lymphoid lineage includ-(RT-PCR), Southern blotting and fluorescence in situ hybridizing CD3, CD4, CD8, CD10, CD19 were absent or weakly ation (FISH) with an MLL-specific yeast artificial chromosome expressed. Myeloperoxidase activity was weakly detected on (YAC) probe, suggests the overall incidence of MLL rearrangethe fresh leukemic blasts. Despite receiving chemotherapy, he ment in AML-M5 may be as high as 60%. 3 It was apparent in succumbed to rapidly progressive leukemia on 15 August that study that approximately half the cases with MLL 1995. rearrangement went undetected by cytogenetic methods, including a cryptic t(6;11)(q27;q23) resulting from a cytogenetically invisible insertion juxtaposing AF6 and MLL.Materials and methods A case of AML-M5a with de novo MLL-AF9 fusion evolving from MDS with trisomy 8 present at all phases has recently Cell culture been described. 4 We describe a pair of cell lines, MOLM-13 During relapse, after chemotherapy, a heparinized peripheral blood specimen, obtained with informed consent, was proCorrespondence: Y Matsuo,

Inhibition of NEMO, the regulatory subunit of the IKK complex, induces apoptosis in high-risk myelodysplastic syndrome and acute myeloid leukemia

“…A very similar peptide when fused to the antennapedia cell-permeable sequence (RQ1KIWFQNRRMKWKK) enters cells and inhibits the IKK-dependent NF-kB transactivation (Agou et al, 2004a). We tested the effect of the NEMO peptide on the myelomonocytic P39 cell line (Figure 1a and b), which has been derived from the BM of a MDS/AML patient (Nagai et al, 1984), as well as on the MOLM13 cell line (Figure 1d and e), which has been derived from the peripheral blood of a patient with post-MDS AML (Matsuo et al, 1997). When P39 or MOLM13 cells were cultured in the presence of NEMO peptide, they readily lost their mitochondrial transmembrane potential (DC m ), as determined with the DC m sensitive fluorochrome 3,3 0 dihexyloxacarbocyanine iodide (DiOC 6 (3)) (Metivier et al, 1998), and permeabilized their plasma membranes, as determined with the vital dye propidium iodide (PI) (Figure 1a and d).…”

NF-κB inhibition sensitizes to starvation-induced cell death in high-risk myelodysplastic syndrome and acute myeloid leukemia

“…A representative karyotype of cell line could be: 46, XY, add(6)(q23), add(8)(q24), add(9)(p24), del(9)(p11), add(10)(p14), À16, þ mar. MOLM13 cells (Matsuo et al, 1997) were purchased from the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ). P39 and MOLM13 cells were cultured in RPMI 1640 (GibcoBRL Life Technologies, Carlsbad, CA, USA), supplemented with 10% heat-inactivated FCS, 2 mM L-glutamine (Eurobio, Courtaboeuf, France), 100 IU/ml penicillin and 100 g/ml streptomycin as described NF-jB-dependent sensitization to starvation C Fabre et al (Hassan et al, 1999;Braun et al, 2006a).…”

Down-regulation of MLL-AF9, MLL and MYC expression is not obligatory for monocyte-macrophage maturation in AML-M5 cell lines carrying t(9;11)(p22;q23)

“…457,2000). The aim of the present study was to clarify the pattern of MLL-AF9, MLL and MYC expression after induction of monocyte-macrophage terminal differentiation in THP-1, MM6 and MOLM-13, all of which are AML-M5 cell lines carrying t(9;11)(p22;q23) and expressing MLL-AF9 (5,11,12).…”