Lymphoblastic Leukemia, Acute, With Lymphomatous Features

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Patients with acute lymphoblastic leukemia (ALL) who present with bulky disease of the lymph nodes, spleen, and mediastinum, so-called lymphomatous ALL (LALL), appear clinically to represent a distinct category of ALL of T-cell lineage. The biologic basis of this distinction was pointed out by Chilcote et al. (1985) who found that 6 of 8 patients with clinical features of LALL had karyotypic abnormalities leading to loss of bands 9p22-p21. The mechanisms varied and included deletions, unbalanced translocations, and loss of the entire chromosome. Only 1 of 57 patients without LALL had an abnormality of chromosome 9 at diagnosis. Loss of a 'suppressor' gene (RB1; 614041) comparable to that in retinoblastoma (180200) was postulated. A relationship to methylthioadenosine phosphorylase (156540) was postulated because the structural gene for this enzyme maps to the same region and patients with LALL may lack this enzyme in malignant cells during relapse. Lymphoblasts lacking this enzyme are unable to salvage adenine and methionine and are therefore especially sensitive to inhibitors of de novo purine synthesis (Kamatani et al., 1981). Kowalczyk and Sandberg (1981) had earlier found changes in 9p in a subgroup of ALL cases. Chilcote et al. (1985) pointed out that there is a fragile site at 9p21 and raised the question of familial predisposition on this basis. (This fragile site is the breakpoint in the translocation t(9;11)(p21-22;q23), which is associated with acute nonlymphocytic leukemia with monocytic features, ANLL-AMoL-M5a.) The aunt of one of the patients of Chilcote et al. (1985) had died as a child from ALL with lymphomatous features. If the analogy to RB1 holds, there is the same dilemma as to whether this should be called dominant or recessive; by the Chilcote hypothesis, it is presumably recessive. In a large series, Murphy et al. (1985) confirmed an abnormality of 9p in 10 to 11% of cases (33 out of more than 300) of acute lymphoblastic leukemia. The breakpoints in 9p clustered in the p22-p21 region. They could not, however, corroborate the specific association with T-cell origin or so-called lymphomatous clinical features.

(Although to our knowledge not the determinant of an inherited phenotype, dominant or recessive, LALL appears to be a specific DNA coding segment that is involved in causation of a specific neoplasm through somatic cell mutation.)