Detection of tryptase in cytoplasmic granules of basophils in patients with chronic myeloid leukemia and other myeloid neoplasms

Samorapoompichit, Puchit; Kiener, Hans P.; Schernthaner, Gerit‐Holger; Jordan, John-Hendrik; Agis, Hermine; Wimazal, Friedrich; Baghestanian, Mehrdad; Rezaie-Majd, Abdolreza; Sperr, Wolfgang R.; Lechner, Klaus; Valent, Peter

doi:10.1182/blood.v98.8.2580

Cited by 50 publications

(46 citation statements)

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“…Apoptosis was defined according to conventional cytomorphologic criteria (cell shrinkage, condensation of chromatin structure). 40 To confirm apoptosis in HMC-1 cells, electron microscopy was performed as described, 41,42 using HMC-1 cells (both subclones) exposed to PKC412 (500 nM, 900 nM, or 1 M), AMN107 (1 M), imatinib (1 M), or control medium for 24 hours. After incubation, cells were washed and fixed in 2% paraformaldehyde, 2.5% glutaraldehyde, and 0.025% CaCl 2 buffered in 0.1 M sodium cacodylate buffer (pH 7.4) for 1 hour.…”

Section: Evaluation Of Apoptosis By Conventional Morphology and Electmentioning

confidence: 99%

PKC412 inhibits in vitro growth of neoplastic human mast cells expressing the D816V-mutated variant of KIT: comparison with AMN107, imatinib, and cladribine (2CdA) and evaluation of cooperative drug effects

Gleixner

Mayerhofer

Aichberger

et al. 2006

Blood

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Section: Evaluation Of Apoptosis By Conventional Morphology and Electmentioning

confidence: 99%

PKC412 inhibits in vitro growth of neoplastic human mast cells expressing the D816V-mutated variant of KIT: comparison with AMN107, imatinib, and cladribine (2CdA) and evaluation of cooperative drug effects

Gleixner

Mayerhofer

Aichberger

et al. 2006

Blood

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“…Sections were contrasted in uranyl acetate and lead citrate, and viewed in a JEOL 1200-EX-II transmission electron microscope (JEOL, Tokyo, Japan). [53][54][55] To further confirm apoptosis in HMC-1 cells exposed to PEG-ZnPP or SMA-ZnPP (10 M; 72 hours), a TUNEL assay was performed using the in situ cell death detection kit-fluorescein (Roche) as reported. 55,56 Cells were analyzed with a Nikon Eclipse-E-800 fluorescence microscope (Tokyo, Japan).…”

Section: Evaluation Of Apoptosis By Microscopy and Tunel Assaymentioning

confidence: 99%

“…Apoptotic cells 52 were quantified on Wright-Giemsa-stained cytospin preparations. To confirm apoptosis, electron microscopy was performed as described [53][54][55] using HMC-1 cells exposed to SMA-ZnPP (10 M) for 72 hours. After fixation, cells were washed, suspended in agar, "postfixed" in 1.3% OsO 4 , and stained en bloc in 2% uranyl acetate and sodium maleate buffer.…”

Section: Evaluation Of Apoptosis By Microscopy and Tunel Assaymentioning

confidence: 99%

Identification of heat shock protein 32 (Hsp32) as a novel survival factor and therapeutic target in neoplastic mast cells

Kondo¹,

Gleixner²,

Mayerhofer³

et al. 2007

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Systemic mastocytosis (SM) is a myeloid neoplasm characterized by increased survival and accumulation of neoplastic mast cells (MCs). In most patients, the D816V-mutated variant of KIT is detectable. We report here that heat shock protein 32 (Hsp32), also known as heme oxygenase-1 (HO-1), is a novel KIT-inducible survival factor in neoplastic IntroductionSystemic mastocytosis (SM) is a myeloid neoplasm characterized by increased survival and accumulation of neoplastic mast cells (MCs) in internal organs. [1][2][3][4][5] Indolent and aggressive variants of SM have been described. [1][2][3][4][5][6][7] In patients with aggressive SM (ASM) or MC leukemia (MCL), the response to conventional drugs is poor, and the prognosis is grave. [4][5][6][7] These patients are candidates for cytoreductive or experimental therapy. [4][5][6][7][8][9][10] Indeed, several attempts have been made to identify novel therapeutic targets in neoplastic MCs. 4,5,[8][9][10] In most patients with SM, including those with ASM or MCL, the KIT mutation D816V is detectable. [5][6][7][11][12][13][14][15] This mutation is associated with ligand-independent activation of KIT. 16 Therefore, a number of attempts have been made to identify drugs interfering with the tyrosine kinase (TK) activity of KIT D816V. 9,10,[17][18][19][20][21] One of these drugs is PKC412, which counteracts in vitro growth of neoplastic MCs harboring KIT D816V. 17,18 In addition, PKC412 was found to inhibit growth of neoplastic MCs in a patient with MCL. 19 However, despite its impressive effects, PKC412 alone may not be sufficient to induce long-lasting complete responses in ASM/MCL. 19 Therefore, current research focuses on additional drug targets in neoplastic MCs and respective targeted drugs. 9 One attractive type of target are the survival factors expressed in neoplastic MCs.Heat shock protein 32 (Hsp32), also known as heme oxygenase-1 (HO-1), is a stress-related survival factor [22][23][24] that is expressed constitutively in various neoplastic cells. [25][26][27][28][29][30][31] Thus, whereas previous studies have pointed to the protective role of Hsp32 in mesenchymal cells in inflammatory reactions and the related stress response, [22][23][24] more recent data suggest that neoplastic cells also use Hsp32 as a survival-related molecule. [25][26][27][28][29][30][31] Moreover, Hsp32-targeting drugs have been described as counteracting in vivo growth of experimental tumors in mice. [25][26][27] We have recently shown that Hsp32/HO-1 is constitutively expressed in neoplastic cells in chronic myeloid leukemia (CML), and that the CMLspecific oncoprotein BCR-ABL promotes expression of Hsp32. 29 With regard to MCs, little is known about the expression of Hsp32. In rats, normal tissue MCs express low baseline levels of Hsp32, and its expression may increase after cell activation. 32 It has also been shown that activated rat MCs can use Hsp32 as a cytoprotective survival factor. 32 So far, however, expression of Hsp32 has not been examined in the context of mastocytosis. In the...

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“…Most important prognostic histopathologic variables in MDS are the presence of AMA-CD34 (increase in CD34+ cells), marked BM fibrosis, and an overt [54]. Aberrant expression of CD25 in BM mast cells has also been described.…”

Section: Impact Of Histopathology In the Prognostication Of Mdsmentioning

confidence: 99%

Standards and Impact of Hematopathology in Myelodysplastic Syndromes (MDS)

et al. 2010

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AbstrAct:The diagnosis, classification, and prognostication of patients with myelodysplastic syndromes (MDS) are usually based on clinical parameters, analysis of peripheral blood and bone marrow smears, and cytogenetic determinants. However, a thorough histologic and immunohistochemical examination of the bone marrow is often required for a final diagnosis and exact classification in these patients. Notably, histology and immunohistology may reveal dysplasia in megakaryocytes or other bone marrow lineages and/or the presence of clusters of CD34-positive precursor cells. In other cases, histology may reveal an unrelated or co-existing hematopoietic neoplasm, or may support the conclusion the patient is suffering from acute myeloid leukemia rather than MDS. Moreover, histologic investigations and immunohistology may reveal an increase in tryptase-positive cells, a coexisting systemic mastocytosis, or bone marrow fibrosis, which is of prognostic significance. To discuss diagnostic algorithms, terminologies, parameters, and specific issues in the hematopathologic evaluation of MDS, a Working Conference involving a consortium of US and EU experts, was organized in June 2010. The outcomes of the conference and resulting recommendations provided by the faculty, are reported in this article. These guidelines should assist in the diagnosis, classification, and prognostication in MDS in daily practice as well as in clinical trials.

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Detection of tryptase in cytoplasmic granules of basophils in patients with chronic myeloid leukemia and other myeloid neoplasms

Cited by 50 publications

References 22 publications

PKC412 inhibits in vitro growth of neoplastic human mast cells expressing the D816V-mutated variant of KIT: comparison with AMN107, imatinib, and cladribine (2CdA) and evaluation of cooperative drug effects

PKC412 inhibits in vitro growth of neoplastic human mast cells expressing the D816V-mutated variant of KIT: comparison with AMN107, imatinib, and cladribine (2CdA) and evaluation of cooperative drug effects

Identification of heat shock protein 32 (Hsp32) as a novel survival factor and therapeutic target in neoplastic mast cells

Standards and Impact of Hematopathology in Myelodysplastic Syndromes (MDS)

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