Stem cell self-renewal is regulated by intrinsic mechanisms and extrinsic signals mediated via specialized microenvironments called “niches.” The best-characterized stem cell is the hematopoietic stem cell (HSC). Self-renewal and differentiation ability of HSC are regulated by two major elements: endosteal and vascular regulatory elements. The osteoblastic niche localized at the inner surface of the bone cavity might serve as a reservoir for long-term HSC storage in a quiescent state. Whereas the vascular niche, which consists of sinusoidal endothelial cell lining blood vessel, provides an environment for short-term HSC proliferation and differentiation. Both niches act together to maintain hematopoietic homeostasis. In this paper, we provide some principles applying to the hematopoietic niches, which will be useful in the study and understanding of other stem cell niches. We will discuss altered microenvironment signaling leading to myeloid lineage disease. And finally, we will review some data on the development of acute myeloid leukemia from a subpopulation called leukemia-initiating cells (LIC), and we will discuss on the emerging evidences supporting the influence of the microenvironment on chemotherapy resistance.

Introduction Ibrutinib is an oral inhibitor of Bruton’s tyrosine kinase that is used for a variety of B cell hematological malignancies. Skin and subcutaneous tissue manifestations have been reported and were witnessed in up to 32% of the patients on ibrutinib. The mechanism in which ibrutinib can cause skin toxicities has been thought due to the inhibition of epidermal growth factor; c-Kit and platelet-derived growth factor receptor). Here, we report a case of an elderly chronic lymphocytic leukemia patient who developed multiple inflamed lesions and lower limb cellulitis in 100 days after initiating ibrutinib therapy. Case report A 68-year-old male patient with relapsed chronic lymphocytic leukemia was started on ibrutinib 420 mg orally daily following multiple lines of therapy. Three months following ibrutinib, the patient developed multiple hyper pigmented lesions over both forearms then over both thighs; buttocks and lower limbs. The lesions were labeled as ecthyma and cellulitis that started as papules, which progressed to pustules. Management and outcomes The patient required admission in which he received prolonged course of antibiotics. Biopsy from the wound showed soft tissue fragment infiltrated by acute and chronic inflammatory cells with necrosis; rare foreign body giant cells and granulation tissue formation; suggestive of abscess. Subsequently, ibrutinib was stopped permanently. Discussion This is the first case description of an ibrutinib-associated sever skin toxicity in Qatar. The provided information regarding the clinical descriptions of toxicity profiles in general and skin-based in particular is valuable information for daily clinical practice, especially when selecting the optimum first-line treatment for the patient.

Thalassemia syndrome has diverse clinical presentations and a global spread that has far exceeded the classical Mediterranean basin where the mutations arose. The mutations that give rise to either alpha or beta thalassemia are numerous, resulting in a wide spectrum of clinical severity ranging from carrier state to life-threatening, inherited hemolytic anemia that requires regular blood transfusion. Beta thalassemia major constitutes a remarkable challenge to health care providers. The complications arising due to the anemia, transfusional iron overload, as well as other therapy-related complications add to the complexity of this condition. To produce this consensus opinion manuscript, a PubMed search was performed to gather evidence-based original articles, review articles, as well as published work reflecting the experience of physicians and scientists in the Arabian Gulf region in an effort to standardize the management protocol.