Acute Promyelocytic Leukemia and Chronic Lymphocytic Leukemia: Concomitant Presentation of Two Molecularly Distinct Entities.

Acute myeloid leukemia (AML) developing in patients with chronic lymphocytic leukemia (CLL) is very uncommon and usually associated with prior treatment. Acute promyelocytic leukemia (APL) accounts for a very small proportion of treatment-associated AML. So far, there has been only one reported case of APL occurring post radiation for prostate cancer in a patient with CLL. We report herein the first case of APL and CLL presenting concomitantly in an untreated patient. Evaluation of peripheral blood and bone marrow aspirate with immunohistochemistry, flow cytometry, and FISH to confirm two morphologically, molecularly and genetically distinct leukemic populations characteristic of APL and CLL is required. APL is a hematologic emergency, and aggressive management is vital to a successful therapeutic outcome. Standard treatment is with All-trans retinoic acid (ATRA) and anthracycline-based regimen, whether the process is de novo or therapy-related. Due to increased incidence of secondary malignancies in CLL patients, active surveillance is necessary.

Charcot's osteoarthropathy mimicking an osteosarcoma of humerus.

Charcot's arthropathy or neuropathic osteoarthropathy is a form of destructive arthropathy associated with decreased sensory innervation. We present an unusual case of a patient referred to oncology clinic for further evaluation of a spindle cell neoplasm of the humerus concerning for malignancy. The mass presented as a lytic lesion associated with a right humerus fracture. This was later diagnosed as Charcot's shoulder secondary to cervical syringomyelia. A detailed case report and discussion are presented here.

Synthesis and cancer stem cell-based activity of substituted 5-morpholino-7H-thieno[3,2-b]pyran-7-ones designed as next generation PI3K inhibitors.

Dysregulation of the phosphatidylinositol-3-kinase (PI3K) pathway in a wide range of tumors has made PI3K a consensus target to inhibit as illustrated by more than 15 inhibitors now in clinical trials. Our previous work, built on the early pioneering multikinase inhibitor LY294002, resulted in the only PI3K vascular-targeted PI3K inhibitor prodrug, SF1126, which has now completed Phase I clinical trials. This inhibitor has properties that impart more in vivo activity than should be warranted by its enzymatic potency, which in general is much lower than other clinical stage PI3K inhibitors. We embarked on the exploration of scaffolds that retained such properties while simultaneously exhibiting an increased potency toward PI3K. This work resulted in the discovery of the 5-morpholino-7H-thieno[3,2-b]pyran-7-one system as the foundation of a new compound class of potential PI3K inhibitors having improved potency toward PI3K. The synthesis and cancer stem cell-based activity of these compounds are reported herein.