Table 1.
Demographic and main clinical and biological features of the MM patients at diagnosis.
Fig 1.
SHP-1 and SHP-2 gene expression in bone marrow plasma cells isolated from MM patients and healthy donors.
(A, B) Statistical dot plots showing the mRNA levels of SHP-1 and SHP-2 relative to the endogenous gene RPLP0 in sorted bone marrow plasma cells of healthy controls (HC, n = 16) and multiple myeloma patients (MM, n = 45). (C) Correlation between SHP-1 and SHP-2 relative gene expression within MM bone marrow plasma cells. Spearman rank correlation (r) and p values are indicated.
Fig 2.
SOCS-1 gene expression in bone marrow plasma cells isolated from MM patients and healthy donors.
(A) Statistical dot plots showing the mRNA levels of SOCS-1 relative to the endogenous gene RPLP0 in sorted bone marrow plasma cells of healthy controls (HC, n = 16) and MM patients (MM, n = 45). (B, C) Correlation between SOCS-1 and SHP-1, SOCS-1 and SHP-2 relative gene expression in MM bone marrow plasma cells. Spearman rank correlation (r) and p values are indicated.
Fig 3.
SHP-1 and SHP-2 gene expression inversely correlate with the level of bone marrow infiltration.
(A) Correlation between bone marrow infiltration and the relative gene expression of SHP-1, SHP-2 and SOCS-1 in the sorted bone marrow plasma cells. Spearman rank correlation (r) and p values are indicated. (B) The degree of bone marrow infiltration is compared in patients exhibiting normal or decreased expression of SHP-1, SHP-2 and SOCS-1 genes. P values are indicated.
Fig 4.
Gene expression of SHP-1, SHP-2 and SOCS-1 according to the degree of bone marrow infiltration.
(A, B) The relative gene expression of SHP-1, SHP-2 and SOCS-1 was compared in patients subdivided according to two different thresholds (20% and 30%) of bone marrow infiltration. P values are indicated.
Fig 5.
Gene expression of SHP-1, SHP-2 and SOCS-1 according to the percent reduction of the monoclonal component.
(A) Correlation between the reduction of the serum monoclonal component (M-component) and the relative expression of SHP-1, SHP-2 and SOCS-1 in sorted bone marrow plasma cells. Spearman rank correlation (r) and p values are indicated. (B) Levels of reduction in the serum M-component are compared between patients exhibiting normal or reduced expression of SHP-1, SHP-2 and SOCS-1. P values are indicated. (C) The relative gene expression of SHP-1, SHP-2 and SOCS-1 was compared between the two patient subgroups with a decrease in the M-component <90% or ≥90%. P values are indicated.
Table 2.
Numbers of “non-responders” (patients with partial or no response) and “responders” (patients with either complete or very good partial response) in “reduced expression” or “normal expression” groups for each of the studied gene.
P values are indicated.
Fig 6.
Relationship between treatment response and the global gene expression score.
(A) The graph recapitulates the correlation between the global score for SHP-1, SHP-2 and SOCS-1 gene expression and the percent reduction in the serum monoclonal component (M-component). Spearman rank correlation (r) and p values are indicated. (B) The global expression score of SHP-1, SHP-2 and SOCS-1 genes was compared between the two patient subgroups with a M-component reduction level <90% or ≥90%. P values are indicated.
Fig 7.
Relationship between the activation of the JAK/STAT pathway and the gene expression of SHP-1, SHP-2 and SOCS-1.
(A) Consecutive sections of paraffin-embedded MM bone marrow biopsies (40x magnification) were stained with rabbit anti-human p-STAT3 or isotype control. Representative samples are shown from 4 MM patients displaying a score of 0, 1, 2 and 3 (no p-STAT3 staining, weak p-STAT3 staining, intermediate p-STAT3 staining and strong pSTAT3 staining, respectively). (B) The graph recapitulates the correlation between the global score of SHP-1, SHP-2 and SOCS-1 gene expression and the score for p-STAT3 staining intensity. Spearman rank correlation (r) and p values are indicated.
Table 3.
SHP-1, SHP-2 and SOCS-1 gene expression profiles and the corresponding Immunohistochemistry (IHC) scores for p-STAT3 staining in the indicated patients.