MODE OF TRANSMISSION & PATHOPHYSIOLOGY

Transmission

             HTLV-I propagated in IMR90 human diploid fibroblasts was transmitted to human myeloid leukemia HL60 cells at a low efficiency. After co-cultivation for 3 months, the viral genome was detected in 14/48 HL60 cell clones. Among the 14 HTLV-I-infected clones, 8 contained subgenomic fragments alone or in addition to the complete HTLV-I genome. The frequency of deleted proviruses (9/24 total proviruses) was unexpectedly high. Hirt's supernatant of some of the clones harboring complete HTLV-I genome(s) in the chromosome contained both linear and circular HTLV-I proviral DNAs. The circular DNAs were composed of one LTR and 2 LTR closed circular proviruses. These clones produced infectious HTLV-I constitutively, which was proved by transmission of the viral genome into fresh IMR90 cells by co-cultivation. However, in these clones, re-integration of extrachromosomal provirus into their own chromosomes was not observed.

Pathophysiology

       Leukemia is malignant neoplasms of the cells derived from either the myeloid or lymphoid line of the hematopoietic stem cells in the bone marrow. Proliferating abnormal and immature cells (blast) spill out into the blood and infiltrate the spleen, lymph nodes, and other tissue. Acute leukemias are characterized by rapid progression of symptoms. High numbers (greater than 50,000/mm3) of circulating blast weaken blood vessel walls, with high risk for rupture and bleeding, including intracranial hemorrhage.Lymphocytic leukemias involve immature lymphocytes and their progenitors. They arise in the bone marrows but infiltrate the spleen, lymph nodes, central nervous system (CNS), and other tissues. Myelogenous leukemias involve the pluripotent myeloid stem cells and, thus, interfere with the maturation of granulocytes, erythrocytes, and thrombocytes. Acute myelogenous leukemias (AML) and acute lymphatic leukemia (ALL) have similar presentations and courses. Approximately half of new leukemias are acute. Approximately 85 % of acute leukemias in adults are AML, and incidence of AML increases with age. ALL is the most common cancer in children, with peak incidence between ages 2 and 9.
Although the cause of leukemias is unknown, predisposing factors include genetic susceptibility, exposure to ionizing radiation or certain chemicals and toxins, some genetic disorder (Down syndromes, Fanconi’s anemia), and human T-cell leukemia-lymphoma virus. Complications include infection, leukostasis leading to hemorrhage, renal failure, tumor lysis syndrome, and disseminating intravascular coagulation.