It has been revealed that the Wnt/&#x3b2;-catenin signaling pathway plays an important role in the development of solid tumors and hematological malignancies, particularly in B-cell neoplasia and leukemia. In the last decade there have been made experimental approaches targeting the Wnt pathway in chronic leukemia. In this paper we provide an overview about the current state of knowledge regarding the Wnt/&#x3b2;-catenin signaling pathway in chronic leukemia with special focus on therapeutic options and strategies.

S. Thanendrarajan

Y. Kim

I. G. H. Schmidt-Wolf

Understanding and Targeting the Wnt/&#x3b2;-Catenin Signaling Pathway in Chronic Leukemia

Recent studies have shown genetic and epigenetic aberrations resulting in aberrant activation of the Wingless-Int (Wnt) pathway, thus influencing the initiation and progression of acute myeloid leukemia (AML). Of major importance, these findings may lead to novel treatment strategies exploiting targeted modulation of Wnt signaling. This paper comprises the latest status of knowledge concerning the role of Wnt pathway alteration in AML and outlines future lines of research and their clinical perspectives.

Wnt/ß-Catenin: A New Therapeutic Approach to Acute Myeloid Leukemia

Among herpesviruses, &#x3b3;-herpesviruses are supposed to have typical oncogenic activities. Two human &#x3b3;-herpesviruses, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), are putative etiologic agents for Burkitt lymphoma, nasopharyngeal carcinoma, and some cases of gastric cancers, and Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma (PEL) especially in AIDS setting for the latter case, respectively. Since such two viruses mentioned above are highly species specific, it has been quite difficult to prove their oncogenic activities in animal models. Nevertheless, the viral oncogenesis is epidemiologically and/or in vitro experimentally evident. This time, we investigated gene expression profiles of KSHV-oriented lymphoma cell lines, EBV-oriented lymphoma cell lines, and T-cell leukemia cell lines. Both KSHV and EBV cause a B-cell-originated lymphoma, but the gene expression profiles were typically classified. Furthermore, KSHV could govern gene expression profiles, although PELs are usually coinfected with KSHV and EBV.

Keiji Ueda

Eriko Ohsaki

Kazushi Nakano

Xin Zheng

Characterization of Kaposi&#39;s Sarcoma-Associated Herpesvirus-Related Lymphomas by DNA Microarray Analysis

The t(9;22)(q34;q11) translocation is found in about 90% of chronic myeloid leukemia (CML) patients.  About 5–10% of CML patients have complex variant translocations involving a third chromosome in addition to chromosomes 9 and 22.  Herein, we describe a CML-chronic phase male with a complex translocation involving chromosome 16, t(9;22;16)(q34;q11;q24). First, he was treated with interferon-alpha and intermittent hydroxyurea, but only a partial cytogenetic response was attained.  Subsequently, the patient was treated with imatinib mesylate because of an additional chromosome abnormality, trisomy 8. A major molecular response was obtained after one year's imatinib therapy, and the follow-up chromosomal analysis performed 4 years and 3 months after the initiation of imatinib therapy displayed a normal karyotype of 46,XY.

Masahiro Manabe

Yumi Yoshii

Satoru Mukai

Erina Sakamoto

Hiroshi Kanashima

Takeshi Inoue

Hirofumi Teshima

A Rare t(9;22;16)(q34;q11;q24) Translocation in Chronic Myeloid Leukemia for Which Imatinib Mesylate Was Effective: A Case Report


		Myeloid Sarcoma may occur in patients with an acute or chronic myeloproliferative disorder  as well as de novo, with no apparent sign or symptom of concomitant haematological disease. The patients are preferentially young male and the site of disease localization may vary from central nervous system to pleura and thorax, with a common involvement of the reticuloendothelial system. The disease often shows chromosomal rearrangements, involving chromosomes 7, 8 and 3 and sometimes a complex karyotype (more than 3 abnormalities) is detected at diagnosis. The prognosis of this disease is dismal and only high-dose chemotherapy with autologous or allogeneic stem cells transplantation (auto or allo-SCT) may be potentially curative. In the absence of definitive elements that can define the prognosis of extra-medullary localization of &#x201c;standard risk&#x201d; AML, Clinicians should pursue the collection of data from different Centres and design of homogeneous treatment strategies, that could integrate standard chemotherapy with specific approaches, such as radiotherapy, transplant procedures or, in selected cases (such as those displaying molecular abnormalities involving protein tyrosine-kinases), molecularly targeted therapies.

M. Malagola

M. Tiribelli

D. Russo

A. Candoni

G. Visani

A. Isidori

Myeloid Sarcoma: The Clinician&#39;s Point of View

Algae preparations are commonly used in alternative medicine. We examined the effects of algae extracts on normal hematopoietic cells and leukemia cells. Ethanol extracts were prepared of Dunaliella salina (Dun), Astaxanthin (Ast), Spirulina platensis (Spir), and Aphanizomenon flos-aquae (AFA). Cell viability effects were completed by Annexin staining. Ast and AFA inhibited HL-60 and MV-4-11 whereas Dun and Spir had no effect. Primary AML blasts demonstrated increased apoptosis in AFA. Primary CLL cells showed apoptosis at 24 hours after exposure to Dun, Ast, Spir, and AFA. High AFA concentrations decreased viability of normal marrow cells. Normal <svg style="vertical-align:-0.46123pt;width:43.1875px;" id="M1" height="10.175" version="1.1" viewBox="0 0 43.1875 10.175" width="43.1875" xmlns="http://www.w3.org/2000/svg">
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			</svg> viability was inhibited by Dun. Dun and AFA inhibited BFU-E, but all extracts inhibited CFU-GM. Cell-cycle analysis of AML cell lines showed G0/G1 arrest in the presence of AFA. These data suggest that algae extracts may inhibit AML cell lines and leukemia blasts, but they may also have potential inhibitory effects on normal hematopoiesis.

Jeremy Bechelli

Myra Coppage

Karen Rosell

Jane Liesveld

Cytotoxicity of Algae Extracts on Normal and Malignant Cells

Myeloid sarcoma (MS) is a neoplasm of immature granulocytes, monocytes, or both involving any extramedullary site. Twenty one patients with MS at diagnosis who were treated at King Hussein Cancer Center in Jordan were included in this retrospective study with a male to female ratio of 2&#x02009;:&#x02009;1. The most common site was the reticuloendothelial system. The most common morphology subtype was M2 (38&#37;) and the most frequent chromosomal abnormality was trisomy 8. Twenty patients received induction chemotherapy; only 14 (70&#37;) achieved complete remission. Median survival time was 24.7 months for the whole group and 58.6 months for patients who underwent allogenic bone marrow transplant. This paper showed that MS has frequent M2 morphology, carries chromosomal aberrations other than t(8;21), and requires aggressive therapy as a front line approach.

Hani Al-Khateeb

Ahmed Badheeb

Husam Haddad

Lina Marei

Salah Abbasi

Myeloid Sarcoma: Clinicopathologic, Cytogenetic, and Outcome Analysis of 21 Adult Patients

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Leukemia Research and Treatment