[Successful treatment with rituximab in a patient with splenic marginal zone B-cell lymphoma accompanied by cold agglutinin disease].

An 81-year-old man was admitted to our hospital due to dyspnea in July 2008. A physical examination revealed marked splenomegaly, and the results of laboratory tests were as follows: hemoglobin (Hb)=7.0 g/dL, Ret=6.

Non-secretory immunoglobulin E myeloma associated with immunoglobulin G monoclonal gammopathy of undetermined significance.

A 68-year old woman came to our hospital with a severe case of anemia. Serum immunoelectropheresis identified a monoclonal immunoglobulin (Ig) G and κ protein. The serum IgE level was within the nomal range and the amounts of remaining immunogloblins were low.

Regulation and importance of the PI3K/Akt/mTOR signaling pathway in hematologic malignancies.

Phosphatidylinositol 3-kinase (PI3K), a heterodimeric lipid kinase, is a key enzyme in signal transduction from various stimuli to downstream pathways that elicit diverse responses involving growth, proliferation, survival, differentiation, and metabolism in many cellular systems. Activated PI3K generates phosphatidylinositol-3,4,5-triphosphate, which recruits phosphatidylinositol-dependent kinase 1 (PDK1) and Akt serine/threonine kinase at the plasma membrane, resulting in activation of Akt. In turn, Akt activates multiple downstream targets, most notably the mTOR pathway.

The PI3K/Akt pathway as a target in the treatment of hematologic malignancies.

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway plays a central role in growth, proliferation, and anti-apoptotic mechanisms to promote cell cycle and survival not only in normal cells but also in a variety of tumor cells. Thus, the PI3K/Akt pathway, including the downstream effectors, may be a critical target for cancer therapy. Although this pathway has been investigated rigorously and dissected in detail in many physiological systems, its role in molecular target therapy for cancer remains to be established.

[2-year complete remission after withdrawal of methotrexate in a rectal methotrexate-associated diffuse large B-cell lymphoma].

A 71-year-old man, who had been receiving methotrexate (MTX) and prednisolone for the treatment of rheumatoid arthritis, was admitted to our hospital in August of 2004 with rectal hemorrhage. Histological examination of an ulcerative lesion of the rectum revealed diffuse large B-cell lymphoma (DLBCL). Chemotherapy with the CHOP regimen with dose reduction following cessation of MTX was initiated.

Acquired factor V inhibitor responsive to corticosteroids in a patient with double cancers.

A 70-year-old woman suffering from HCV-related liver cirrhosis was admitted for abnormal bleeding. Laboratory findings included PT at 46.6 sec, APTT at >212 sec, factor V activity of <3%, and factor V inhibitor of 2 BU.

Therapy-related myelodysplastic syndrome with monosomy 5 after successful treatment of acute myeloid leukemia (M2).

We describe a patient who developed myelodysplastic syndrome over 2 years after achieving complete remission of acute myeloid leukemia (AML). The patient was treated in July 1998 with anthracycline, etoposide, and behenoyl cytarabine chemotherapy for AML (French-American-British classification, M2; World Health Organization classification, AML with maturation) and achieved complete remission. At presentation, no chromosomal abnormalities were detected.

[Pure red cell aplasia occurring during the course of chronic myelogenous leukemia].

The patient was a 47-year-old man who was diagnosed in 1989 as having chronic myelogenous leukemia (CML). He had been treated with interferon-alpha (IFN-alpha) and hydroxyurea. In August 1999, he was admitted to our hospital for examination of severe anemia and increased platelet count.

Involvement of Akt kinase in the action of STI571 on chronic myelogenous leukemia cells.

To elucidate the role of mitogen-activated protein kinases (MAPKs) and Akt kinase in leukemogenesis caused by the breakpoint cluster region (BCR)-Abelson (ABL) tyrosine kinase oncoprotein, we examined the activities of MAPKs and Akt kinase and their roles in the action of STI571, a specific inhibitor of BCR-ABL tyrosine kinase, in chronic myelogenous leukemia (CML) cells. We found that extracellular signal-regulated kinase (ERK) 1/2 and Akt kinase are constitutively active in the chronic phase of CML, blast crisis of CML, and the CML-derived K562 cell line. Both interferon-alpha and STI571 suppressed ERK1/2 activity in K562 cells.

[Successful use of etoposide in an elderly patient with chronic recurrent hemophagocytic syndrome].

A 66-year-old man was admitted to our hospital for fever on January 19, 1998. He began showing periodic high fever in June 1997 and an increased serum LDH in August 1997. His history included surgery for esophageal cancer in 1993.

Activation of extracellular signal-regulated kinase through B-cell antigen receptor in B-cell chronic lymphocytic leukemia.

B-cell chronic lymphocytic leukemia (B-CLL) cells express on their surface membranes immunoglobulin (Ig) M or IgD, both of which normally function as B-cell antigen receptors (BCRs). However, in contrast to normal B-cells, in B-CLL cells several important signaling pathways, such as the activation of protein tyrosine kinase via BCR, are defective. We have examined whether the activities of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), p38 MAPK, and Akt kinase, are functional in B-CLL cells, because these kinases play critical roles in activation in response to BCR stimulation, tumor cell growth, and survival.