Hematologic malignancies are cancers of the blood and bone marrow, including leukemia and lymphoma. Leukemia is a malignant neoplasm characterized by abnormal proliferation of leukocytes and is one of the four major types of cancer. Leukemia is diagnosed in about 29,000 adults and 2,000 children each year in the United States. Leukemias are classified according to the type of leukocyte most prominently involved. Acute leukemias are predominantly undifferentiated cell populations and chronic leukemias have more mature cell forms.
The acute leukemias are divided into lymphoblastic (ALL) and non-lymphoblastic (ANLL) types and may be further subdivided by morphologic and cytochemical appearance according to the French-American-British classification or according to their type and degree of differentiation. Specific B- and T-cell, as well as myeloid cell surface markers/antigens are used in the classification too. ALL is predominantly a childhood disease while acute myeloid leukemia (AML), is a more common acute leukemia among adults.
Chronic leukemias are divided into lymphocytic (CLL) and myeloid (CML) types. CLL is characterized by the increased number of mature lymphocytes in blood, bone marrow, and lymphoid organs. Most CLL patients have clonal expansion of lymphocytes with B cell characteristics. CLL is a disease of older persons. In CML, the granulocytic cells predominate at all stages of differentiation in blood and bone marrow, but may also affect liver, spleen, and other organs.
In patients with AML the immature myeloid, erythroid or megakaryotic cells severely outnumber erythrocytes (red blood cells) leading to fatigue and bleeding, and also to increased susceptibility to infection. In children as well as in adults AML has a poor prognosis despite the use of aggressive chemotherapeutic protocols. Overall survival rates are 40-60%. Autologous bone marrow transplant preceded by myeloablative chemotherapy does not change the survival but an allogeneic bone marrow transplant preceded by aggressive chemotherapy might increase the survival rates up to 70%. Unfortunately, the availability of a matched sibling donor is limited.
Among patients with leukemia there can be a highly variable clinical course as reflected by varying survival times and resistance to therapy. Reliable individual diagnostic and prognostic tools are limited at present. For example, there are several diagnostic or prognostic markers for AML, such as CD13, CD33, CD14, CD34, CD117 and CD7. However, the usefulness of these molecules as diagnostic and prognostic markers is limited because the association of these markers with AML has not been consistent (Mason et al., 2006). Accordingly, there remains a need for diagnostic and prognostic tools and for new treatments for leukemia.
The identification of cell types that play an integral role in pathological changes associated with diseased blood vessels such as intimal thickening, the formation of atherosclerotic plaque, in processes of plaque stabilization or rupture that results in obstructive thrombi, have been the subject of several investigations over the last two decades. However, in these pathogenic processes the characteristics of many of the molecular signals that drive migration and recruitment of cells into different vascular compartments are not clear.
A role for proliferation of precursor vascular smooth muscle cells in the genesis of atherosclerotic lesions has been reported (Ross and Glomset, 1973). The migration of blood-borne cells into the endothelium, neointima and media of atherosclerotic plaque has also been described in mouse models of vascular injury (Campbell et al, 2001). However, the mechanism for this is unclear.
Wound healing is the process through which the repair of damaged tissue(s) is accomplished. The wound healing process is comprised of three different stages, referred to as inflammation, granulation tissue formation, and matrix formation and remodelling. The healing process following trauma is an essential quality of and mechanism for life. Healing is associated with the migration into a lesion of blood-borne multi-potential precursor cells.
There is a need for new diagnostic tools and treatments for diseases in blood-borne precursor cells play a role. More particularly, there remains a need for diagnostic and prognostic tools and treatments for leukemia, and a need for further methods of diagnosing, treating and/or preventing diseased or damaged tissue such as cardiovascular disease, as well as methods of stimulating wound healing.