High Serum Interleukin‐2 Levels in Acute Myeloid Leukaemia (Aml) Are Associated With Fab M4 and M5 Subtypes

Cimino, Giuseppe; Sgadari, Cecilia; Amadori, Sergio; Magliocca, Vittoria; Poti, Gian Piero; Cimino, Gaetano; Mandelli, Franco

doi:10.1111/j.1365-2141.1989.tb07774.x

Cited by 4 publications

(3 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A high release of proteases and protease inhibitors was also associated with monocytic differentiation [ 51 ]. Similar observations have also been made in other studies describing the increased release of CXCL8/IL8 [ 54 ], high expression of VEGF [ 52 ] and increased serum levels of IL2 [ 53 ] for patients with monocytic AML cells.…”

Section: Monocytic Fab-m4/m5 Aml Cell Differentiation: Morphological ...supporting

confidence: 88%

“…However, the profile of expressed cytokine receptors differs between patients, and monocytic AML cells seem to express significantly higher levels of receptors for the hematopoietic growth factors GM-CSF (granulocyte-macrophage colony-stimulating factor) and Flt3 ligand and lower levels of SCF (stem cell factor) receptors [ 48 ]. AML cells also show a constitutive release of a wide range of mediators, including CCL and CXCL chemokines, interleukins, hematopoietic growth factors, angioregulatory vascular endothelial growth factor (VEGF), proteases and protease inhibitors [ 49 , 50 , 51 , 52 , 53 , 54 ]. Several of these cytokines thus function as autocrine growth factors.…”

Section: Monocytic Fab-m4/m5 Aml Cell Differentiation: Morphological ...mentioning

confidence: 99%

See 1 more Smart Citation

Monocytic Differentiation in Acute Myeloid Leukemia Cells: Diagnostic Criteria, Biological Heterogeneity, Mitochondrial Metabolism, Resistance to and Induction by Targeted Therapies

Bruserud,

Selheim,

Hernandez-Valladares

et al. 2024

IJMS

View full text Add to dashboard Cite

We review the importance of monocytic differentiation and differentiation induction in non-APL (acute promyelocytic leukemia) variants of acute myeloid leukemia (AML), a malignancy characterized by proliferation of immature myeloid cells. Even though the cellular differentiation block is a fundamental characteristic, the AML cells can show limited signs of differentiation. According to the French–American–British (FAB-M4/M5 subset) and the World Health Organization (WHO) 2016 classifications, monocytic differentiation is characterized by morphological signs and the expression of specific molecular markers involved in cellular communication and adhesion. Furthermore, monocytic FAB-M4/M5 patients are heterogeneous with regards to cytogenetic and molecular genetic abnormalities, and monocytic differentiation does not have any major prognostic impact for these patients when receiving conventional intensive cytotoxic therapy. In contrast, FAB-M4/M5 patients have decreased susceptibility to the Bcl-2 inhibitor venetoclax, and this seems to be due to common molecular characteristics involving mitochondrial regulation of the cellular metabolism and survival, including decreased dependency on Bcl-2 compared to other AML patients. Thus, the susceptibility to Bcl-2 inhibition does not only depend on general resistance/susceptibility mechanisms known from conventional AML therapy but also specific mechanisms involving the molecular target itself or the molecular context of the target. AML cell differentiation status is also associated with susceptibility to other targeted therapies (e.g., CDK2/4/6 and bromodomain inhibition), and differentiation induction seems to be a part of the antileukemic effect for several targeted anti-AML therapies. Differentiation-associated molecular mechanisms may thus become important in the future implementation of targeted therapies in human AML.

show abstract

Section: Monocytic Fab-m4/m5 Aml Cell Differentiation: Morphological ...supporting

confidence: 88%

Section: Monocytic Fab-m4/m5 Aml Cell Differentiation: Morphological ...mentioning

confidence: 99%

Monocytic Differentiation in Acute Myeloid Leukemia Cells: Diagnostic Criteria, Biological Heterogeneity, Mitochondrial Metabolism, Resistance to and Induction by Targeted Therapies

Bruserud,

Selheim,

Hernandez-Valladares

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…Our present study strongly indicates TANAKA 198 that the expression of IL-2RP subunit is more dominant than that of IL-2Ra subunit on AML blast cells and that the presence of IL-2RP is associated with the effect of IL-2 stimulation on leukemic cells. Cimino et al (1989) recently analyzed IL-2 serum levels in 41 AML patients. Serum IL-2 levels were found to be significantly higher in M4 and M5 AML as compared with either normal control or other FAB subtypes.…”

Section: Discussionmentioning

confidence: 99%

Growth of Certain Myeloid Leukemic Cells Can be Stimulated by Interleukin-2

Tanaka

1991

Growth Factors

View full text Add to dashboard Cite

The effect of recombinant interleukin-2 (IL-2) on the proliferation of T-cell depleted leukemic blasts was evaluated in 23 patients with acute myelogenous leukemia (AML). For this purpose, the effect of IL-2 on cell growth, [3H]-thymidine incorporation into the blasts and the expression of IL-2 receptors on cell surface using T-cell depleted blasts were studied. The results showed that IL-2 stimulated [3H]-thymidine incorporation significantly in blasts of 8 out of 23 cases of AML. An IL-2 induced increase in cell number was directly demonstrated in seven out of eight IL-2 responsive patients studied. IL-2 stimulated the proliferation of blasts in monocytic lineage (M4 and M5), but not all M4/M5 leukemics responded to rIL-2. Stimulation of the growth of leukemic cells was not correlated with the expression of Tac antigen on the cell surface, but it was significantly correlated with the expression of IL-2 receptor (IL-2R) beta chain on the cell surface. These results indicate that IL-2 is an active growth factor in certain myeloid leukemia cells, especially of monocytic type.

show abstract

Induction of Tissue Factor by Interleukin-2 in Acute Myelogenous Leukemia (AML) Cells

Tanaka

Kishi

1990

Growth Factors

View full text Add to dashboard Cite

We investigated the induction of tissue factor by lymphokines in human monoblastic leukemia cell lines (U937) and leukemic cells from AML (acute myelogenous leukemia) patients. After incubation for 24 h, IL-2 enhanced the intracellular tissue factor 15-fold with U937 cells, and GM-CSF enhanced it 6-fold. In contrast, other lymphokines, such as IL-1-alpha, IL-1-beta, IL-3, IL-4 and G-CSF, did not affect the activity of tissue factor. The leukemic blasts, depleted of T-lymphocytes, taken from five out of 16 AML patients showed a 2.5-14-fold increase in the activity of tissue factor per cell following incubation with 200 u/ml of IL-2 for 72 h. The IL-2 induced tissue factor activity more markedly than GM-CSF. Tissue factor stimulation by IL-2 did not correlate with the expression of the IL-2 receptor, Tac, but correlated well with FAB classification of AML cells. IL-2 responders were found in M4 and M5 subtypes only, but not all M4/M5 leukemias responded to IL-2. These findings indicate that IL-2 can mediate the tissue factor induction in the monocytic type of AML and the effect is not mediated by Tac receptors. This may shed a new light on our understanding of hypercoagulability in acute monoblastic leukemia.

show abstract

High Serum Interleukin‐2 Levels in Acute Myeloid Leukaemia (Aml) Are Associated With Fab M4 and M5 Subtypes

Cited by 4 publications

References 3 publications

Monocytic Differentiation in Acute Myeloid Leukemia Cells: Diagnostic Criteria, Biological Heterogeneity, Mitochondrial Metabolism, Resistance to and Induction by Targeted Therapies

Monocytic Differentiation in Acute Myeloid Leukemia Cells: Diagnostic Criteria, Biological Heterogeneity, Mitochondrial Metabolism, Resistance to and Induction by Targeted Therapies

Growth of Certain Myeloid Leukemic Cells Can be Stimulated by Interleukin-2

Induction of Tissue Factor by Interleukin-2 in Acute Myelogenous Leukemia (AML) Cells

Contact Info

Product

Resources

About