Page 24 - 2018_11-Haematologica-web

M. Arock et al.
Table 2. Expression of activation-induced antigens, cytokine receptors and molecular targets† by the human mastocytosis-like mast cell lines.
CD Name HMC-1 ROSAKIT D816V MCPV-1.1
Table 3. Expression of lineage-related markers and adhesion mole- cules† by the human mastocytosis-like mast cell lines.
CD16 FcγRIII _ _ _ CD2 LFA2 +
n.t. _
_ _
+ _ n.t. _ + _ + _ + _ n.t. _ + _ n.t. _ n.t. _ _ _ _ _ _ _ n.t. + _ _ + _ + + + + + + + _ n.t. + + _ _ + _ _ _ _ _ _ _ _ _ _ _ _ _ + _ _
FcεRII _ DPP4 _ TNFRSF7 _ FcγRII + MIRL + LAMP-3 + FcγRI _ BGP-1 +
_ _
CD3
CD4
CD5
CD8
CD9
CD10
CD14
CD15
CD17
CD19
CD20
CD22
CD24
CD31
CD38
CD45
CD48
CD50
CD54
CD56
CD58
CD90
CD96
CD133
CD134
CD144
CD146
CD150
CD153
CD166
CD326
TCR _ T4 _ T1_ T8 _
MRP-1 +
CALLA _
LPSR _
LeX _
LacCer _
B4 _
B1 _
SIGLEC-2 _
BA-1 +
PECAM-1 +
T10 _
LCA +
BLAST1 +
ICAM-3 +
ICAM-1 +
NCAM _
LFA-3 +
THY1 _
TACTILE _
AC133 _
OX-40 _
VE-CADHERIN _
MUC18 _
SLAM _
CD30L _
ALCAM +
EPCAM _
CD23
CD26
CD27
CD32
CD59
CD63
CD64
CD66a
CD69
CD71 TfR1 + CD95 FAS +
n.t. n.t. + n.t. + +/- + + + _ _ _ _ _ _ n.t. n.t.
_ _ + + + _ _ + + + _ +/- _ _ _ + +/-
CD Name HMC-1
ROSAKIT D816V
MCPV-1.1
AIM +/-
CD105
CD114
CD115
CD116
CD127
CD129
CD135
CD138
CD164
CD184
CD203c
CD213a1
CD218a
CD243
CD304
CD309 VEGFR2 _
ENDOGLIN _ G-CSFR _ M-CSFR _
GM-CSFRa _ IL-7R _ IL-9R _ FLT3 _
SYND1 _ MGC-24 +
_ _ +/- + n.t. _
+ + _ _ _ _
n.t. _
n.t. +
_ _
CXCR4 +/-
ENPP3 _ IL-13Ra1 _ IL-18Ra _ MDR-1 _ NRP1 _
†some of the related antigens are also listed in Table 4. n.t.: not tested; +: strong expres- sion; +/-: weak expression; -: no expression.
tively phosphorylated. In addition, both subclones remained, as expected, sensitive to the growth inhibitory effects of imatinib (unpublished observations). These addi- tional data demonstrate that ROSA cells are reasonable tools for investigating the oncogenic potential of newly discovered KIT mutants as well as for screening for their sensitivity to TKI.
The MCPV-1 subclones
The human MCPV-1 subclones (MCPV-1.1 through - 1.4) were generated from cord blood-derived CD34+ pro- genitors by culturing these cells with SCF and interleukin- 6 for 8 weeks and then stably transducing HRAS G12V, SV40 TAg and TERT.16 Single-cell clones were then isolat- ed and cultured for more than 2 years to demonstrate immortalization. Light microscopy of Wright-Giemsa- stained MCPV-1.1 cells reveals large, immature cells with bi-, tri-, or multi-lobed (often cloverleaf-like-shaped) nuclei characteristic of MC precursors.16 MCPV-1 cells contain a basophilic cytoplasm, cytoplasmic protrusions and sparse granulation. Moreover, MCPV-1.1 cells exhibit an immunophenotype consistent with MC progenitors (Tables 2 and 3).16 MCPV-1 cells express tryptase but lack
†some of the related antigens are also listed in Table 4. n.t.: not tested; +: strong expres- sion; +/-: weak expression; -: no expression.
surface FcεRI.16 MCPV-1 cells grow independently of SCF and produce a MCL-like disease in NSG mice.
Human mast cell leukemia-like cell lines as models for in vitro testing of growth-inhibiting drugs
Treatment of ISM mainly aims at symptomatic relief of MC mediator symptoms.40 By contrast, treatment of advanced SM is challenging and relies principally on non- targeted and/or targeted cytoreductive therapy.41 In unusual cases (rare KIT-mutant forms or WT KIT) the dis- ease may respond to imatinib or masitinib.30,42,43 In a sub- group of patients with slowly progressing ASM, low-dose prednisolone and interferon-a may be efficacious.44 In addition, low-dose methylprednisolone and cyclosporine A may show some (usually minor) effects in ASM patients.45 Cladribine (2CdA) is often recommended as first-line therapy in patients with advanced SM with multi-organ involvement and slow progression.46,47 A
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haematologica | 2018; 103(11)