A novel myeloid cell line, Marimo, derived from therapy-related acute myeloid leukemia during treatment of essential thrombocythemia: Consistent chromosomal abnormalities and temporary C-MYC gene amplification

Yoshida, Hitoshi; Kondō, Makoto; Ichihashi, Takuji; Hashimoto, Naoya; Inazawa, J; Ohno, Ryuzo; Naoe, Tomoki

doi:10.1016/s0165-4608(97)00017-4

Cited by 21 publications

(10 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using MARIMO cells, an AML cell line harboring abnormal complex karyotypes, PF‐913 treatment induced minimal cell death accompanied by a reduction in the relative quiescent cell population (Fig. S4).…”

Section: Resultsmentioning

confidence: 99%

Small‐molecule Hedgehog inhibitor attenuates the leukemia‐initiation potential of acute myeloid leukemia cells

et al. 2016

Self Cite

View full text Add to dashboard Cite

Aberrant activation of the Hedgehog signaling pathway has been implicated in the maintenance of leukemia stem cell populations in several model systems. PF‐04449913 (PF‐913) is a selective, small‐molecule inhibitor of Smoothened, a membrane protein that regulates the Hedgehog pathway. However, details of the proof‐of‐concept and mechanism of action of PF‐913 following administration to patients with acute myeloid leukemia (AML) are unclear. This study examined the role of the Hedgehog signaling pathway in AML cells, and evaluated the in vitro and in vivo effects of the Smoothened inhibitor PF‐913. In primary AML cells, activation of the Hedgehog signaling pathway was more pronounced in CD34+ cells than CD34− cells. In vitro treatment with PF‐913 induced a decrease in the quiescent cell population accompanied by minimal cell death. In vivo treatment with PF‐913 attenuated the leukemia‐initiation potential of AML cells in a serial transplantation mouse model, while limiting reduction of tumor burden in a primary xenotransplant system. Comprehensive gene set enrichment analysis revealed that PF‐913 modulated self‐renewal signatures and cell cycle progression. Furthermore, PF‐913 sensitized AML cells to cytosine arabinoside, and abrogated resistance to cytosine arabinoside in AML cells cocultured with HS‐5 stromal cells. These findings imply that pharmacologic inhibition of Hedgehog signaling attenuates the leukemia‐initiation potential, and also enhanced AML therapy by sensitizing dormant leukemia stem cells to chemotherapy and overcoming resistance in the bone marrow microenvironment.

show abstract

Section: Resultsmentioning

confidence: 99%

Small‐molecule Hedgehog inhibitor attenuates the leukemia‐initiation potential of acute myeloid leukemia cells

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…10 Another type 1 mutant, del61 CALR, reported in the MARIMO cell line, 30 derived from an ET patient who was treated with Busulfan, 43 also activates TpoR (supplemental Figure 2A-B). Mutants that preserve stretches of negativelycharged residues like ins5 do not show calcium defects.…”

Section: Discussionmentioning

confidence: 99%

Thrombopoietin receptor activation by myeloproliferative neoplasm associated calreticulin mutants

Chachoua

Pecquet

El-Khoury

et al. 2016

Blood

280

369

View full text Add to dashboard Cite

show abstract

“…The only cell line found to harbor a CALR mutation was MARIMO, originally derived from a 68-year-old female with AML-M2, and an antecedent history of ET. 7 MARIMO is negative for JAK2V617F and MPL exon 10 mutations (data not shown) and carries a heterozygous 61-basepair (bp) deletion in CALR exon 9 (c.1099_1159del; L367fs*43), which, like all other reported CALR mutations, results in a +1- bp shift in the reading frame and thus generates a novel C terminus ( Figure 1a ). In patients, the commonest two CALR mutations, accounting for 85% of cases, are a 52-bp deletion (type 1; c.1099_1150del; L367fs*46) and a 5-bp insertion (type 2; c.1154_1155_ins; K385fs*47).…”

mentioning

confidence: 85%

MARIMO cells harbor a CALR mutation but are not dependent on JAK2/STAT5 signaling

et al. 2014

View full text Add to dashboard Cite

A novel myeloid cell line, Marimo, derived from therapy-related acute myeloid leukemia during treatment of essential thrombocythemia: Consistent chromosomal abnormalities and temporary C-MYC gene amplification

Cited by 21 publications

References 11 publications

Small‐molecule Hedgehog inhibitor attenuates the leukemia‐initiation potential of acute myeloid leukemia cells

Small‐molecule Hedgehog inhibitor attenuates the leukemia‐initiation potential of acute myeloid leukemia cells

Thrombopoietin receptor activation by myeloproliferative neoplasm associated calreticulin mutants

MARIMO cells harbor a CALR mutation but are not dependent on JAK2/STAT5 signaling

Contact Info

Product

Resources

About