Editorial

4 pages, 178 KiB

Open AccessEditorial

by Yoichi Imai

Cancers 2020, 12(9), 2544; https://doi.org/10.3390/cancers12092544 - 07 Sep 2020

Cited by 3 | Viewed by 2012

Specialists in the field of multiple myeloma (MM) research have written a series of 12 articles (2 original articles, 10 reviews) in the Special Issue “Latest Development in Multiple Myeloma” [...] Full article

(This article belongs to the Special Issue Latest Development in Multiple Myeloma)

Research

Jump to: Editorial, Review

16 pages, 1118 KiB

Open AccessArticle

Efficacy and Safety of High-Dose Chemotherapy with Treosulfan and Melphalan in Multiple Myeloma

by Cédric Gillich, Dilara Akhoundova, Michael Hayoz, Yolanda Aebi, Carlo R. Largiadèr, Katja Seipel, Michael Daskalakis, Ulrike Bacher and Thomas Pabst

Cancers 2023, 15(10), 2699; https://doi.org/10.3390/cancers15102699 - 10 May 2023

Viewed by 1324

Abstract

(1) Background: Upfront treatment consolidation with high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) has relevantly contributed to achieving durable remissions following induction treatment in multiple myeloma (MM) patients. The optimization of HDCT regimens can, therefore, essentially contribute to improving the depth [...] Read more.

(1) Background: Upfront treatment consolidation with high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) has relevantly contributed to achieving durable remissions following induction treatment in multiple myeloma (MM) patients. The optimization of HDCT regimens can, therefore, essentially contribute to improving the depth and duration of tumor remissions. To date, melphalan at 200 mg/m² is the standard HDCT regimen for fit MM patients. In our previous work, we showed promising efficacy and safety results for treosulfan (14 g/m²) and melphalan (200 mg/m²) (TreoMel) in acute myeloid leukemia (AML) patients receiving ASCT. Based on these data, TreoMel became the standard of care for fit MM patients at our institution. (2) Methods: We identified 115 consecutive MM patients who underwent consolidation with TreoMel between 01/2020 and 08/2022 at the University Hospital of Bern. We analyzed the safety and efficacy data, as well as the treosulfan pharmacokinetics, correlating them with tumor responses. (3) Results: A complete response (CR) rate of 84% was achieved, which is comparable to the CR rate reported for the quadruplet combination. The median PFS was 30 months (95% CI: 20.4—not reached), and the 31-month OS rate was 83%. The median area under the curve (AUC) for treosulfan was 952.5 mg*h/L (range: 527.4–1781.4), and the median peak level was 332.3 mg/L (range: 168–554). The treosulfan pharmacokinetics showed no significant correlation with MM responses after HDCT and ASCT. However, female patients had a significantly higher AUC (p = 0.007) and peak value (p = 0.001), and the higher values were associated with longer hospitalizations. (4) Conclusions: Treatment consolidation with TreoMel HDCT demonstrated a promising efficacy and safety profile in our cohort of MM patients and deserves further investigation in prospective studies. Full article

(This article belongs to the Special Issue Latest Development in Multiple Myeloma)

► Show Figures

Figure 1

18 pages, 6168 KiB

Open AccessArticle

Exon-4 Mutations in KRAS Affect MEK/ERK and PI3K/AKT Signaling in Human Multiple Myeloma Cell Lines

by Susann Weißbach, Sofia Catalina Heredia-Guerrero, Stefanie Barnsteiner, Lukas Großhans, Jochen Bodem, Hanna Starz, Christian Langer, Silke Appenzeller, Stefan Knop, Torsten Steinbrunn, Simone Rost, Hermann Einsele, Ralf Christian Bargou, Andreas Rosenwald, Thorsten Stühmer and Ellen Leich

Cancers 2020, 12(2), 455; https://doi.org/10.3390/cancers12020455 - 16 Feb 2020

Cited by 8 | Viewed by 5039

Abstract

Approximately 20% of multiple myeloma (MM) cases harbor a point mutation in KRAS. However, there is still no final consent on whether KRAS-mutations are associated with disease outcome. Specifically, no data exist on whether KRAS-mutations have an impact on survival [...] Read more.

Approximately 20% of multiple myeloma (MM) cases harbor a point mutation in KRAS. However, there is still no final consent on whether KRAS-mutations are associated with disease outcome. Specifically, no data exist on whether KRAS-mutations have an impact on survival of MM patients at diagnosis in the era of novel agents. Direct blockade of KRAS for therapeutic purposes is mostly impossible, but recently a mutation-specific covalent inhibitor targeting KRAS^p.G12C entered into clinical trials. However, other KRAS hotspot-mutations exist in MM patients, including the less common exon-4 mutations. For the current study, the coding regions of KRAS were deep-sequenced in 80 newly diagnosed MM patients, uniformely treated with three cycles of bortezomib plus dexamethasone and cyclophosphamide (VCD)-induction, followed by high-dose chemotherapy and autologous stem cell transplantation. Moreover, the functional impact of KRAS^p.G12A and the exon-4 mutations p.A146T and p.A146V on different survival pathways was investigated. Specifically, KRAS^WT, KRAS^p.G12A, KRAS^p.A146T, and KRAS^p.A146V were overexpressed in HEK293 cells and the KRAS^WT MM cell lines JJN3 and OPM2 using lentiviral transduction and the Sleeping Beauty vector system. Even though KRAS-mutations were not correlated with survival, all KRAS-mutants were found capable of potentially activating MEK/ERK- and sustaining PI3K/AKT-signaling in MM cells. Full article

(This article belongs to the Special Issue Latest Development in Multiple Myeloma)

► Show Figures

Figure 1

11 pages, 634 KiB

Open AccessArticle

Polyclonal Immunoglobulin Recovery after Autologous Stem Cell Transplantation Is an Independent Prognostic Factor for Survival Outcome in Patients with Multiple Myeloma

by Shuji Ozaki, Takeshi Harada, Hikaru Yagi, Etsuko Sekimoto, Hironobu Shibata, Toshio Shigekiyo, Shiro Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa and Masahiro Abe

Cancers 2020, 12(1), 12; https://doi.org/10.3390/cancers12010012 - 18 Dec 2019

Cited by 6 | Viewed by 3144

Abstract

We retrospectively analyzed multiple myeloma (MM) patients who underwent autologous stem cell transplantation (ASCT) without maintenance therapy to assess the impact of recovery of normal immunoglobulin (Ig) on clinical outcomes. The recovery of polyclonal Ig was defined as normalization of all values of [...] Read more.

We retrospectively analyzed multiple myeloma (MM) patients who underwent autologous stem cell transplantation (ASCT) without maintenance therapy to assess the impact of recovery of normal immunoglobulin (Ig) on clinical outcomes. The recovery of polyclonal Ig was defined as normalization of all values of serum IgG, IgA, and IgM 1 year after ASCT. Among 50 patients, 26 patients showed polyclonal Ig recovery; 14 patients were in ≥complete response (CR) and 12 remained in non-CR after ASCT. The patients with Ig recovery exhibited a significantly better progression-free survival (PFS, median, 46.8 vs. 26.7 months, p = 0.0071) and overall survival (OS, median, not reached vs. 65.3 months, p < 0.00001) compared with those without Ig recovery. The survival benefits of Ig recovery were similarly observed in ≥CR patients (median OS, not reached vs. 80.5 months, p = 0.061) and non-CR patients (median OS, not reached vs. 53.2 months, p = 0.00016). Multivariate analysis revealed that non-CR and not all Ig recovery were independent prognostic factors for PFS (HR, 4.284, 95%CI (1.868–9.826), p = 0.00059; and HR, 2.804, 95%CI (1.334–5.896), p = 0.0065, respectively) and also for OS (HR, 8.245, 95%CI (1.528–44.47), p = 0.014; and HR, 36.55, 95%CI (3.942–338.8), p = 0.0015, respectively). Therefore, in addition to the depth of response, the recovery of polyclonal Ig after ASCT is a useful indicator especially for long-term outcome and might be considered to prevent overtreatment with maintenance therapy in transplanted patients with MM. Full article

(This article belongs to the Special Issue Latest Development in Multiple Myeloma)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

17 pages, 1126 KiB

Open AccessReview

Targeting Multiple Myeloma through the Biology of Long-Lived Plasma Cells

by Adam Utley, Brittany Lipchick, Kelvin P. Lee and Mikhail A. Nikiforov

Cancers 2020, 12(8), 2117; https://doi.org/10.3390/cancers12082117 - 30 Jul 2020

Cited by 7 | Viewed by 4601

Abstract

Multiple myeloma (MM) is a hematological malignancy of terminally differentiated bone marrow (BM) resident B lymphocytes known as plasma cells (PC). PC that reside in the bone marrow include a distinct population of long-lived plasma cells (LLPC) that have the capacity to live [...] Read more.

Multiple myeloma (MM) is a hematological malignancy of terminally differentiated bone marrow (BM) resident B lymphocytes known as plasma cells (PC). PC that reside in the bone marrow include a distinct population of long-lived plasma cells (LLPC) that have the capacity to live for very long periods of time (decades in the human population). LLPC biology is critical for understanding MM disease induction and progression because MM shares many of the same extrinsic and intrinsic survival programs as LLPC. Extrinsic survival signals required for LLPC survival include soluble factors and cellular partners in the bone marrow microenvironment. Intrinsic programs that enhance cellular fidelity are also required for LLPC survival including increased autophagy, metabolic fitness, the unfolded protein response (UPR), and enhanced responsiveness to endoplasmic reticulum (ER) stress. Targeting LLPC cell survival mechanisms have led to standard of care treatments for MM including proteasome inhibition (Bortezomib), steroids (Dexamethasone), and immunomodulatory drugs (Lenalidomide). MM patients that relapse often do so by circumventing LLPC survival pathways targeted by treatment. Understanding the mechanisms by which LLPC are able to survive can allow us insight into the treatment of MM, which allows for the enhancement of therapeutic strategies in MM both at diagnosis and upon patient relapse. Full article

(This article belongs to the Special Issue Latest Development in Multiple Myeloma)

► Show Figures

Figure 1

32 pages, 1513 KiB

Open AccessEditor’s ChoiceReview

Multiple Myeloma: Available Therapies and Causes of Drug Resistance

by Vanessa Pinto, Rui Bergantim, Hugo R. Caires, Hugo Seca, José E. Guimarães and M. Helena Vasconcelos

Cancers 2020, 12(2), 407; https://doi.org/10.3390/cancers12020407 - 10 Feb 2020

Cited by 131 | Viewed by 19407

Abstract

Multiple myeloma (MM) is the second most common blood cancer. Treatments for MM include corticosteroids, alkylating agents, anthracyclines, proteasome inhibitors, immunomodulatory drugs, histone deacetylase inhibitors and monoclonal antibodies. Survival outcomes have improved substantially due to the introduction of many of these drugs allied [...] Read more.

Multiple myeloma (MM) is the second most common blood cancer. Treatments for MM include corticosteroids, alkylating agents, anthracyclines, proteasome inhibitors, immunomodulatory drugs, histone deacetylase inhibitors and monoclonal antibodies. Survival outcomes have improved substantially due to the introduction of many of these drugs allied with their rational use. Nonetheless, MM patients successively relapse after one or more treatment regimens or become refractory, mostly due to drug resistance. This review focuses on the main drugs used in MM treatment and on causes of drug resistance, including cytogenetic, genetic and epigenetic alterations, abnormal drug transport and metabolism, dysregulation of apoptosis, autophagy activation and other intracellular signaling pathways, the presence of cancer stem cells, and the tumor microenvironment. Furthermore, we highlight the areas that need to be further clarified in an attempt to identify novel therapeutic targets to counteract drug resistance in MM patients. Full article

(This article belongs to the Special Issue Latest Development in Multiple Myeloma)

► Show Figures

Figure 1

19 pages, 734 KiB

Open AccessEditor’s ChoiceReview

Proteasome Inhibitors for the Treatment of Multiple Myeloma

by Shigeki Ito

Cancers 2020, 12(2), 265; https://doi.org/10.3390/cancers12020265 - 22 Jan 2020

Cited by 105 | Viewed by 9946

Abstract

Use of proteasome inhibitors (PIs) has been the therapeutic backbone of myeloma treatment over the past decade. Many PIs are being developed and evaluated in the preclinical and clinical setting. The first-in-class PI, bortezomib, was approved by the US food and drug administration [...] Read more.

Use of proteasome inhibitors (PIs) has been the therapeutic backbone of myeloma treatment over the past decade. Many PIs are being developed and evaluated in the preclinical and clinical setting. The first-in-class PI, bortezomib, was approved by the US food and drug administration in 2003. Carfilzomib is a next-generation PI, which selectively and irreversibly inhibits proteasome enzymatic activities in a dose-dependent manner. Ixazomib was the first oral PI to be developed and has a robust efficacy and favorable safety profile in patients with multiple myeloma. These PIs, together with other agents, including alkylators, immunomodulatory drugs, and monoclonal antibodies, have been incorporated into several regimens. This review summarizes the biological effects and the results of clinical trials investigating PI-based combination regimens and novel investigational inhibitors and discusses the future perspective in the treatment of multiple myeloma. Full article

(This article belongs to the Special Issue Latest Development in Multiple Myeloma)

► Show Figures

Figure 1

18 pages, 958 KiB

Open AccessReview

Pain Management in Patients with Multiple Myeloma: An Update

by Flaminia Coluzzi, Roman Rolke and Sebastiano Mercadante

Cancers 2019, 11(12), 2037; https://doi.org/10.3390/cancers11122037 - 17 Dec 2019

Cited by 36 | Viewed by 7081

Abstract

Most patients with multiple myeloma (MM) suffer from chronic pain at every stage of the natural disease process. This review focuses on the most common causes of chronic pain in MM patients: (1) pain from myeloma bone disease (MBD); (2) chemotherapy-induced peripheral neuropathy [...] Read more.

Most patients with multiple myeloma (MM) suffer from chronic pain at every stage of the natural disease process. This review focuses on the most common causes of chronic pain in MM patients: (1) pain from myeloma bone disease (MBD); (2) chemotherapy-induced peripheral neuropathy as a possible consequence of proteasome inhibitor therapy (i.e., bortezomib-induced); (3) post-herpetic neuralgia as a possible complication of varicella zoster virus reactivation because of post-transplantation immunodepression; and (4) pain in cancer survivors, with increasing numbers due to the success of antiblastic treatments, which have significantly improved overall survival and quality of life. In this review, non-pain specialists will find an overview including a detailed description of physiopathological mechanisms underlying central sensitization and pain chronification in bone pain, the rationale for the correct use of analgesics and invasive techniques in different pain syndromes, and the most recent recommendations published on these topics. The ultimate target of this review was to underlie that different types of pain can be observed in MM patients, and highlight that only after an accurate pain assessment, clinical examination, and pain classification, can pain be safely and effectively addressed by selecting the right analgesic option for the right patient. Full article

(This article belongs to the Special Issue Latest Development in Multiple Myeloma)

► Show Figures

Figure 1

11 pages, 649 KiB

Open AccessReview

Chimeric Antigen Receptor T-Cell Therapy for Multiple Myeloma

by Naoki Hosen

Cancers 2019, 11(12), 2024; https://doi.org/10.3390/cancers11122024 - 15 Dec 2019

Cited by 12 | Viewed by 6236

Abstract

CD19 Chimeric antigen receptor (CAR) T cell therapy has been shown to be effective for B cell leukemia and lymphoma. Many researchers are now trying to develop CAR T cells for various types of cancer. For multiple myeloma (MM), B-cell maturation antigen (BCMA) [...] Read more.

CD19 Chimeric antigen receptor (CAR) T cell therapy has been shown to be effective for B cell leukemia and lymphoma. Many researchers are now trying to develop CAR T cells for various types of cancer. For multiple myeloma (MM), B-cell maturation antigen (BCMA) has been recently proved to be a promising target. However, cure of MM is still difficult, and several other targets, for example immunoglobulin kappa chain, SLAM Family Member 7 (SLAMF7), or G-protein coupled receptor family C group 5 member D (GPRC5D), are being tested as targets for CAR T cells. We also reported that the activated integrin β7 can serve as a specific target for CAR T cells against MM, and are preparing a clinical trial. In this review, we summarized current status of CAR T cell therapy for MM and discussed about the future perspectives. Full article

(This article belongs to the Special Issue Latest Development in Multiple Myeloma)

► Show Figures

Figure 1

38 pages, 600 KiB

Open AccessReview

Pursuing a Curative Approach in Multiple Myeloma: A Review of New Therapeutic Strategies

by Mattia D'Agostino, Luca Bertamini, Stefania Oliva, Mario Boccadoro and Francesca Gay

Cancers 2019, 11(12), 2015; https://doi.org/10.3390/cancers11122015 - 13 Dec 2019

Cited by 26 | Viewed by 6839

Abstract

Multiple myeloma (MM) is still considered an incurable hematologic cancer and, in the last decades, the treatment goal has been to obtain a long-lasting disease control. However, the recent availability of new effective drugs has led to unprecedented high-quality responses and prolonged progression-free [...] Read more.

Multiple myeloma (MM) is still considered an incurable hematologic cancer and, in the last decades, the treatment goal has been to obtain a long-lasting disease control. However, the recent availability of new effective drugs has led to unprecedented high-quality responses and prolonged progression-free survival and overall survival. The improvement of response rates has prompted the development of new, very sensitive methods to measure residual disease, even when monoclonal components become undetectable in patients’ serum and urine. Several scientific efforts have been made to develop reliable and validated techniques to measure minimal residual disease (MRD), both within and outside the bone marrow. With the newest multidrug combinations, a good proportion of MM patients can achieve MRD negativity. Long-lasting MRD negativity may prove to be a marker of “operational cure”, although the follow-up of the currently ongoing studies is still too short to draw conclusions. In this article, we focus on results obtained with new-generation multidrug combinations in the treatment of high-risk smoldering MM and newly diagnosed MM, including the potential role of MRD and MRD-driven treatment strategies in clinical trials, in order to optimize and individualize treatment. Full article

(This article belongs to the Special Issue Latest Development in Multiple Myeloma)

► Show Figures

Figure 1

15 pages, 548 KiB

Open AccessReview

Immunotherapy for Multiple Myeloma

by Hideto Tamura, Mariko Ishibashi, Mika Sunakawa and Koiti Inokuchi

Cancers 2019, 11(12), 2009; https://doi.org/10.3390/cancers11122009 - 12 Dec 2019

Cited by 16 | Viewed by 6942

Abstract

Despite therapeutic advances over the past decades, multiple myeloma (MM) remains a largely incurable disease with poor prognosis in high-risk patients, and thus new treatment strategies are needed to achieve treatment breakthroughs. MM represents various forms of impaired immune surveillance characterized by not [...] Read more.

Despite therapeutic advances over the past decades, multiple myeloma (MM) remains a largely incurable disease with poor prognosis in high-risk patients, and thus new treatment strategies are needed to achieve treatment breakthroughs. MM represents various forms of impaired immune surveillance characterized by not only disrupted antibody production but also immune dysfunction of T, natural killer cells, and dendritic cells, although immunotherapeutic interventions such as allogeneic stem-cell transplantation and dendritic cell-based tumor vaccines were reported to prolong survival in limited populations of MM patients. Recently, epoch-making immunotherapies, i.e., immunomodulatory drug-intensified monoclonal antibodies, such as daratumumab combined with lenalidomide and chimeric antigen receptor T-cell therapy targeting B-cell maturation antigen, have been developed, and was shown to improve prognosis even in advanced-stage MM patients. Clinical trials using other antibody-based treatments, such as antibody drug-conjugate and bispecific antigen-directed CD3 T-cell engager targeting, are ongoing. The manipulation of anergic T-cells by checkpoint inhibitors, including an anti-T-cell immunoglobulin and ITIM domains (TIGIT) antibody, also has the potential to prolong survival times. Those new treatments or their combination will improve prognosis and possibly point toward a cure for MM. Full article

(This article belongs to the Special Issue Latest Development in Multiple Myeloma)

► Show Figures

Figure 1

17 pages, 304 KiB

Open AccessReview

Reactivation of Hepatitis B Virus in Patients with Multiple Myeloma

by Yutaka Tsukune, Makoto Sasaki and Norio Komatsu

Cancers 2019, 11(11), 1819; https://doi.org/10.3390/cancers11111819 - 19 Nov 2019

Cited by 6 | Viewed by 3657

Abstract

Reactivation of hepatitis B virus (HBV) is a well-known complication in patients with hematological malignancies during or after cytotoxic chemotherapy. If the initiation of antiviral therapy is delayed in patients with HBV reactivation, these patients can develop severe hepatitis and may die of [...] Read more.

Reactivation of hepatitis B virus (HBV) is a well-known complication in patients with hematological malignancies during or after cytotoxic chemotherapy. If the initiation of antiviral therapy is delayed in patients with HBV reactivation, these patients can develop severe hepatitis and may die of fulminant hepatitis. The preventive strategy for HBV reactivation in patients with malignant lymphoma has already been established based on some prospective studies. As there was an increased number of novel agents being approved for the treatment of multiple myeloma (MM), the number of reported cases of HBV reactivation among MM patients has gradually increased. We conducted a Japanese nationwide retrospective study and revealed that HBV reactivation in MM patients is not rare and that autologous stem cell transplantation is a significant risk factor. In this study, around 20% of all patients with HBV reactivation developed HBV reactivation after 2 years from the initiation of therapy, unlike malignant lymphoma. This might be due to the fact that almost all of the patients received chemotherapy for a long duration. Therefore, a new strategy for the prevention of HBV reactivation in MM patients is required. Full article

(This article belongs to the Special Issue Latest Development in Multiple Myeloma)

19 pages, 1107 KiB

Open AccessReview

The Role and Function of microRNA in the Pathogenesis of Multiple Myeloma

by Hiroshi Handa, Yuki Murakami, Rei Ishihara, Kei Kimura-Masuda and Yuta Masuda

Cancers 2019, 11(11), 1738; https://doi.org/10.3390/cancers11111738 - 06 Nov 2019

Cited by 64 | Viewed by 5640

Abstract

Recently, attention has been drawn to the role of non-coding regions of the genome in cancer pathogenesis. MicroRNAs (miRNAs) are small non-coding RNAs with 19–25 bases of length that control gene expression by destroying messenger RNA or inhibiting its translation. In multiple myeloma [...] Read more.

Recently, attention has been drawn to the role of non-coding regions of the genome in cancer pathogenesis. MicroRNAs (miRNAs) are small non-coding RNAs with 19–25 bases of length that control gene expression by destroying messenger RNA or inhibiting its translation. In multiple myeloma (MM), the expression of several miRNAs, such as miR-15a and miR-16, is markedly decreased and their target genes upregulated, suggesting their role as tumor-suppressing miRNAs. In contrast, miRNAs such as miR-21 and miR-221 are highly expressed and function as oncogenes (oncomiRs). In addition, several miRNAs, such as those belonging to the miR-34 family, are transcriptional targets of p53 and mediate its tumor-suppressive functions. Many miRNAs are associated with drug resistance, and the modulation of their expression or activity might be explored to reverse it. Moreover, miRNA expression patterns in either MM cells or serum exosomes have been shown to be good prognostic markers. miRNA regulation mechanisms have not been fully elucidated. Many miRNAs are epigenetically controlled by DNA methylation and histone modification, and others regulate the expression of epigenetic modifiers, indicating that miRNA and other epigenetic effectors are part of a network. In this review, we outlined the roles of miRNAs in MM and their potential to predict MM prognosis and develop novel therapies. Full article

(This article belongs to the Special Issue Latest Development in Multiple Myeloma)

► Show Figures

Figure 1

17 pages, 1518 KiB

Open AccessReview

AXL Receptor Tyrosine Kinase as a Therapeutic Target in Hematological Malignancies: Focus on Multiple Myeloma

by Siyang Yan, Niels Vandewalle, Nathan De Beule, Sylvia Faict, Ken Maes, Elke De Bruyne, Eline Menu, Karin Vanderkerken and Kim De Veirman

Cancers 2019, 11(11), 1727; https://doi.org/10.3390/cancers11111727 - 05 Nov 2019

Cited by 19 | Viewed by 5637

Abstract

AXL belongs to the TAM (TYRO3, AXL, and MERTK) receptor family, a unique subfamily of the receptor tyrosine kinases. Their common ligand is growth arrest-specific protein 6 (GAS6). The GAS6/TAM signaling pathway regulates many important cell processes and plays an essential role in [...] Read more.

AXL belongs to the TAM (TYRO3, AXL, and MERTK) receptor family, a unique subfamily of the receptor tyrosine kinases. Their common ligand is growth arrest-specific protein 6 (GAS6). The GAS6/TAM signaling pathway regulates many important cell processes and plays an essential role in immunity, hemostasis, and erythropoiesis. In cancer, AXL overexpression and activation has been associated with cell proliferation, chemotherapy resistance, tumor angiogenesis, invasion, and metastasis; and has been correlated with a poor prognosis. In hematological malignancies, the expression and function of AXL is highly diverse, not only between the different tumor types but also in the surrounding tumor microenvironment. Most research and clinical evidence has been provided for AXL inhibitors in acute myeloid leukemia. However, recent studies also revealed an important role of AXL in lymphoid leukemia, lymphoma, and multiple myeloma. In this review, we summarize the basic functions of AXL in various cell types and the role of AXL in different hematological cancers, with a focus on AXL in the dormancy of multiple myeloma. In addition, we provide an update on the most promising AXL inhibitors currently in preclinical/clinical evaluation and discuss future perspectives in this emerging field. Full article

(This article belongs to the Special Issue Latest Development in Multiple Myeloma)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Latest Development in Multiple Myeloma

Share This Special Issue

Special Issue Editor

Special Issue Information

Published Papers (14 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI