Protein key to control, growth of blood cells

August 14, 2008

Findings may aid in bone marrow transplants, blood diseases

New research sheds light on the biological events by which stem cells in the bone marrow develop into the broad variety of cells that circulate in the blood. The findings may help improve the success of bone marrow transplants and may lead to better treatments for life-threatening blood diseases.

"As we better understand the biological pathways that regulate the growth of stem cells, we may identify new approaches for treating blood disorders," said study leader Wei Tong, Ph.D., a hematology researcher at The Children's Hospital of Philadelphia. Her study appeared online July 10 in the Journal of Clinical Investigation.

Hematopoietic stem cells (HSCs) develop into all types of blood cells: red blood cells, platelets and immune cells. HSCs, like other stem cells, have the ability to self-renew: each can give rise to more mature, developed cells with more specific functions, as well as a new stem cell. (Everyone carries HSCs in their bone marrow, unlike embryonic stem cells, which exist only in embryos.)

In her study, conducted in mice, Tong focused on a protein called Lnk that helps control HSC expansion. When a growth factor in the blood called thrombopoietin (TPO) acts on its cell receptor, it triggers signals along a pathway that includes another protein, JAK2. JAK2, in turn, causes stem cells to increase their numbers.

Tong's group and others previously found that Lnk is a negative regulator for HSCs, acting as a brake on stem cell expansion. In the current study, they found that mice genetically engineered to lack the Lnk protein had 10 times the normal amount of HSCs in their bone marrow. Without Lnk to directly interact with JAK2 and inhibit its activity, TPO made stem cell production go into overdrive.

However, there was an unexpected potential benefit-- the expanded population of stem cells had a higher proportion of quiescent cells, those in a resting stage in the cell cycle. Quiescent stem cells, said Tong, are more likely to succeed in a recipient when they are used in bone marrow transplantation.

Although much research remains to be done, added Tong, other researchers might build on this knowledge to manipulate HSCs for more effective bone marrow transplants for cancer patients after high-dose chemotherapy or radiotherapy. It might also improve treatments for particular blood disorders. For example, aplastic anemia, severe combined immunodeficiency disorders and hemoglobin disorders involve deficiencies of specific immune cells in the blood. Using a drug to inhibit Lnk could potentially produce larger numbers of HSCs for a successful bone marrow transplant.

Myeloproliferative disorders (MPDs), on the other hand, entail the opposite danger-a sometimes-fatal overproduction of certain bone marrow cells. Clinicians might use Tong's research on Lnk and its associated signaling pathway to curtail stem cell production and control MPDs.

Children's Hospital of Philadelphia

---

---

	Bone Marrow Pathology by Barbara J. Bain (Author), David M. Clark (Author), Bridget S. Wilkins (Author) Bone Marrow Pathology has been extensively revised to reflect the significant advances which have occurred in the application of cytogenetics and in particular, molecular genetics in the diagnosis, classification and understanding of haematological disorders. This comprehensive book not only provides information on all common disease entities, but also covers rare disorders in which bone marrow examination is useful. It is designed as practical resource with ‘Problems and Pitfalls’ sections throughout to aid laboratory diagnosis.This fourth edition:Incorporates the recommendations of the 2008 WHO Classification of Tumours of Haematopoietic and Lymphoid TissuesCovers key diagnostic techniques such as flow cytometric immunophenotyping, immunohistochemistry and cytogenetic and molecular...
	Bone Marrow Nei Kung: Taoist Techniques for Rejuvenating the Blood and Bone by Mantak Chia (Author) A guide to nourishing the body through bone marrow rejuvenation exercises • Presents exercises to “regrow” bone marrow, revive the internal organs, and prevent osteoporosis • Explains the use of bone breathing and bone compression, “hitting” to detoxify the body, and sexual energy massage and chi weight lifting to enhance the life force within Most Westerners believe that a daily physical exercise program helps slow the aging process. Yet those whose bodies appear most physically fit on the outside often enjoy only the same life span as the average nonathletic person. It is the internal organs and glands that nourish every function of the body, and it is the bone marrow that nourishes and rejuvenates the organs and glands through the...
	Diagnostic Pathology: Blood and Bone Marrow: Published by Amirsys® by Kathy Foucar (Author) Designed as an easy-to-use and comprehensive reference for the practicing pathologist, Diagnostic Pathology: Blood & Bone Marrow is the newest title in the Diagnostic Pathology series by Amirsys. This extensively illustrated book showcases over 1,900 high-quality images, including gross pathology and a variety of pathology stains. Included are several images that display specialized immunophenotypic and molecular genetic features of bone marrow disorders. As readers have come to expect from Amirsys reference tools, the content is presented in concise, bulleted text that quickly gets to the most critical diagnostic data, including a variety of differential diagnoses. This book pinpoints important elements in the diagnosis of benign and neoplastic disorders and it clearly delineates...
	Bone Marrow Pathology, Third Edition (2 Vol set) by Kathryn Foucar (Author), Kaaren Reichard (Author), David Czuchlewski (Author) The new 2-volume edition of Bone Marrow Pathology is the best of both worlds a comprehensive atlas of diagnostic imaging and illustrations of genetic results combined with practical advice from experts. A virtual roadmap to the latest best practices, the new edition integrates the full scope of the 2008 WHO criteria with answers to your day-to-day diagnostic questions.
	Blood and Bone Marrow Pathology: Expert Consult: Online and Print, 2e by Anna Porwit (Editor), Jeffrey McCullough (Editor), Wendy N Erber MD DPhil FRCPA FRCPath (Editor) Already a standard reference work in the field, the new edition of Blood and Bone Marrow Pathology incorporates the latest WHO classification schemes and the latest ancillary diagnostic techniques in immunohistochemistry and molecular biology in order to provide a comprehensive, well balanced and authoritative guide to the interpretation and diagnosis of neoplastic and non-neoplastic diseases of blood and bone marrow. The text is lavishly illustrated with high quality colour images that demonstrate the relevant pathological,features and immunohistochemical and molecular markers. The text features a well-organized approach that incorporates practical tips and clues to help avoid pitfalls and to ensure optimal diagnosisChapters have been totally rewritten and some new chapters have been...
	Manual of Stem Cell and Bone Marrow Transplantation (Cambridge Medicine) by Joseph H. Antin MD (Author), Deborah Yolin Raley (Author) Over the past 35 years, stem cell and bone marrow transplantation have evolved from experimental therapies to well-established and widely used treatments for a variety of malignant and nonmalignant conditions. This is a practical pocket manual for all members of the stem cell and bone marrow transplant team, based on a popular in-house handbook used at the Dana-Farber Cancer Institute. The manual covers all aspects of the transplantation process, from stem cell processing through management of transplant-related complications. Evaluation and counseling of patients and donors, preventative care, and conditioning regimens are also covered, making this an ideal resource for nurses as well. The text is handily arranged in outline format to maximize the usefulness and convenience of this...
	Atlas of Veterinary Hematology: Blood and Bone Marrow of Domestic Animals by John W. Harvey (Author) This color atlas is designed as a reference for the morphologic aspects of veterinary hematology of common domestic animals. It covers a variety of species, including dogs, cats, horses, cattle, sheep, goats, pigs and llamas. The atlas is divided into two sections, the first covers blood, while the second discusses bone marrow. Techniques for the collection and preparation of blood and bone marrow spears and bone marrow core biopsies are covered in addition to the morphology of the tissues collected. Often, multiple examples of a cell type or abnormal condition are shown to illustrate the variance in morphology.
	Pathology of Bone Marrow by Faramarz Naeim (Author), Naeim (Author) This text provides information on bone marrow pathology. For each disease category featured, the author examines etiology and pathogenesis, pathologic features, clinical aspects, differential diagnosis, and a brief discussion of therapeutic approaches.
	Bone Marrow Nei Kung: Taoist Ways to Improve Your Health by Rejuvenating Your Bone Marrow and Blood by Mantak Chia (Author), Maneewan Chia (Author)
	Bone Marrow and Blood Stem Cell Transplants: A Guide For Patients by Susan Stewart (Author) Bone Marrow and Stem Cell Transplants: A Guide for Patients is the next generation of Susan K. Stewart's groundbreaking 1992 book Bone Marrow Transplants: A Book of Basics for Patients. This new 228 paage guide combines solid medical information with the voices of people who have been through a transplant. Comprehensive and easy-to-read, Bone Marrow and Blood Stem Cell Transplants: A Guide for Patients is a goldmine of information for people considering a transplant with donor marrow or stem cells. The book covers a variety of topics and issues such as; History of Transplantation Nuts and Bolts of a Transplant Choosing a Transplant Center Finding a Stem Cell Donor Being a Donor Emotional/Psychological Considerations When Your Child Needs a Transplant Preparative...