5 results
Search Results
2. Immunophenotypically defined stem cell subsets in paediatric AML are highly heterogeneous and demonstrate differences in BCL‐2 expression by cytogenetic subgroups.
- Author
-
Petersen, Marianne A., Rosenberg, Carina A., Brøndum, Rasmus F., Aggerholm, Anni, Kjeldsen, Eigil, Rahbek, Ole, Ludvigsen, Maja, Hasle, Henrik, Roug, Anne S., and Bill, Marie
- Subjects
STEM cells ,HEMATOPOIETIC stem cells ,ACUTE myeloid leukemia ,CHILD patients ,BONE marrow cells - Abstract
In adult acute myeloid leukaemia (AML), immunophenotypic differences enable discrimination of leukaemic stem cells (LSCs) from healthy haematopoietic stem cells (HSCs). However, immunophenotypic stem cell characteristics are less explored in paediatric AML. Employing a 15‐colour flow cytometry assay, we analysed the expression of eight aberrant surface markers together with BCL‐2 on CD34+CD38− bone marrow stem cells from 38 paediatric AML patients and seven non‐leukaemic, age‐matched controls. Furthermore, clonality was investigated by genetic analyses of sorted immunophenotypically abnormal stem cells from six patients. A total of 50 aberrant marker positive (non‐HSC‐like) subsets with 41 different immunophenotypic profiles were detected. CD123, CLEC12A, and IL1RAP were the most frequently expressed markers. IL1RAP, CD93, and CD25 expression were not restricted to stem cells harbouring leukaemia‐associated mutations. Differential BCL‐2 expression was found among defined cytogenetic subgroups. Interestingly, only immunophenotypically abnormal non‐HSC‐like subsets demonstrated BCL‐2 overexpression. Collectively, we observed pronounced immunophenotypic heterogeneity within the stem cell compartment of paediatric AML patients. Additionally, certain aberrant markers used in adults seemed to be ineligible for detection of leukaemia‐representing stem cells in paediatric patients implying that inference from adult studies must be done with caution. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
3. Identification of patients at high risk of secondary extramedullary multiple myeloma development.
- Author
-
Stork, Martin, Sevcikova, Sabina, Minarik, Jiri, Krhovska, Petra, Radocha, Jakub, Pospisilova, Lenka, Brozova, Lucie, Jarkovsky, Jiri, Spicka, Ivan, Straub, Jan, Pavlicek, Petr, Jungova, Alexandra, Jelinek, Tomas, Sandecka, Viera, Maisnar, Vladimir, Hajek, Roman, and Pour, Ludek
- Subjects
EXTRAMEDULLARY diseases ,PLASMA cell diseases ,DISEASE risk factors ,PLASMACYTOMA ,BONE marrow cells ,MULTIPLE myeloma ,BONE marrow - Abstract
Summary: Multiple myeloma (MM) is characterized by malignant plasma cell infiltration of the bone marrow. In extramedullary multiple myeloma (EMD), a subclone of these cells migrates out of the bone marrow. Out of 4 985 MM patients diagnosed between 2005 and 2017 in the Czech Republic, we analyzed 234 secondary EMD patients to clarify risk factors of secondary EMD development. We found younger age [<65 years; odds ratio (OR) 4·38, 95% confidence interval (CI): 2·46–7·80, P < 0·0001], high lactate dehydrogenase (LDH) levels (>5 μkat/l; OR 2·07, 95% CI: 1·51–2·84, P < 0·0001), extensive osteolytic activity (OR 2·21, 95% CI: 1·54–3·15, P < 0·001), and immunoglobulin A (IgA; OR 1·53, 95% CI: 1·11–2·11, P = 0·009) or the non‐secretory type of MM (OR 2·83; 95% CI: 1·32–6·04, P = 0·007) at the time of MM diagnosis to be the main risk factors for secondary EMD development. Newly diagnosed MM (NDMM) patients with subsequent EMD had inferior median progression‐free (PFS) and overall (OS) survival when compared to NDMM patients without future EMD [mPFS: 13·8 months (95% CI: 11·4–16·3) vs 18·8 months (95% CI: 17·7–19·9), P = 0·006; mOS: 26·7 months (95% CI: 18·1–35·4) vs 58·7 months (95% CI: 54·8–62·6), P < 0·001]. We found that NDMM patients with specific risk factors associated with secondary EMD development have a more aggressive disease course before secondary EMD develops. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
4. An eltrombopag‐induced remission of bone‐marrow aplasia accompanied by marked leukoerythroblastosis and splenomegaly.
- Author
-
Arita, Kotaro, Murakami, Jun, Iwaki, Noriko, Hosono, Naoko, Tasaki, Toshiki, Tsujikawa, Tetsuya, Okazawa, Hidehiko, Imi, Tatsuya, Nannya, Yasuhito, Ogawa, Seishi, and Nakao, Shinji
- Subjects
PURE red cell aplasia ,SOMATIC mutation ,BONE marrow cells ,ERYTHROCYTES ,HEMATOPOIETIC stem cells ,EXTRAMEDULLARY hematopoiesis - Abstract
An eltrombopag-induced remission of bone-marrow aplasia accompanied by marked leukoerythroblastosis and splenomegaly Bone-marrow (BM) failure is caused by various mechanisms, including immune destruction of haematopoietic stem progenitor cells (HSPCs) and intrinsic abnormalities of these cells.1 Although pancytopenia with fatty BM is a sign suggestive of aplastic anaemia (AA), benign BM failure such as AA is commonly ruled out when leukoerythroblastosis is evident in the peripheral blood (PB). This study reports the clinical courses of two recently experienced cases [a 25-year-old woman (Case 1) and a 45-year-old-man (Case 2)] of BM failure, experiencing severe BM aplasia that was associated with marked leukoerythroblastosis in the PB and mild hepatosplenomegaly; a sustained remission of the atypical BM failure was induced by eltrombopag in Case 1. [Extracted from the article]
- Published
- 2022
- Full Text
- View/download PDF
5. More key players in the game for myeloma prognosis and therapy.
- Subjects
OSTEOCLASTS ,MONOCLONAL gammopathies ,TRANCE protein ,CELLULAR recognition ,MULTIPLE myeloma ,BONE marrow cells ,PROGNOSIS - Abstract
Multiple myeloma, inducible T-cell co-stimulator (ICOS), ICOS ligand (ICOSL), soluble ICOS, soluble ICOSL, osteopontin Keywords: multiple myeloma; inducible T-cell co-stimulator (ICOS); ICOS ligand (ICOSL); soluble ICOS; soluble ICOSL; osteopontin EN multiple myeloma inducible T-cell co-stimulator (ICOS) ICOS ligand (ICOSL) soluble ICOS soluble ICOSL osteopontin 1288 1289 2 03/22/22 20220315 NES 220315 INTRODUCTION Multiple myeloma (MM) is a cancer of bone marrow plasma cells that often develops from premalignant monoclonal gammopathy of undetermined significance (MGUS) through an intermediate stage known as smouldering multiple myeloma (SMM).1,2 MGUS and SMM are asymptomatic, whereas symptomatic patients with MM have one or more CRAB criteria (hypercalcaemia, renal failure, anaemia, and/or bone lesions). Inducible T-cell co-stimulator (ICOS) and ICOS ligand are novel players in the multiple-myeloma microenvironment. [Extracted from the article]
- Published
- 2022
- Full Text
- View/download PDF
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.