Cytogenetic findings in chronic myelogenous leukemia

Cytogenetic findings in chronic myeloic leukemia are represented in a survey. More than 90 per cent of CML are characterized by Ph1 chromosomes, with more than 90 per cent of the cases being involved in a translocation (9; 22). Further, non-incidental aberrations are +Ph1, isochromosome (17q) and +8 which particularly develop at the acute stage. Isochromosome 17q is assumed to be a marker for a straightly impending development of a blast crisis. Ph1-negative CML is connected with a comparatively bad prognosis for the patient. Partial trisomy 9q+ is indicated here as a marker chromosome. For the patient concerned congenital chromosome defects, such as the Down-syndrome, represent a higher risk of being affected with leukemia.     

Role of heterochromatin during preferential 9q;22q translocation in chronic myelogenous leukemia

The secondary constriction region (h) of human chromosome 9 was evaluated in 55 chronic myelogenous leukemia (CML) patients with respect to its size and position. Each case was examined by C-banding and distamycin A-4,6-diamidino-2-phenylindole techniques for the expression of the h regions. When one h region of chromosome 9 was larger, it was more frequently involved in the reciprocal translocation with chromosome 22. In addition, there was a higher incidence of pericentric inversions in the h regions in the translocated chromosome 9 when compared with normal homologues. The role of the constitutive heterochromatin of chromosome 9 as a possible influencing factor during 9q;22q translocation in CML is suggested.     

A mathematical model of hematopoiesis--I. Periodic chronic myelogenous leukemia

Periodic chronic myelogenous leukemia (PCML) is an interesting dynamical disease of the hematopoietic system in which oscillating levels of circulating leukocytes, platelets and/or reticulocytes are observed. Typically all of these three differentiated cell types have the same oscillation period, but the relation of the oscillation mean and amplitude to the normal levels is variable. Given the appearance of the abnormal Philadelphia chromosome in all of the nucleated progeny of the hematopoietic stem cells (HSCs), the most parsimonious conclusion is that chronic myelogenous leukemia, and its periodic variant, arise from derangements partially involving the dynamics of the stem cells. Here, we have synthesized several previous mathematical models of HSC dynamics, and models for the regulation of neutrophils, platelets and erythrocytes into a comprehensive model for the regulation of the hematopoietic system. Based on estimates of parameters for a typical normal human, we have systematically explored the changes in some of these parameters necessary to account for the quantitative data on leukocyte, platelet and reticulocyte cycling in 11 patients with PCML. Our results indicate that the critical model parameter changes required to simulate the PCML patient data are an increase in the amplification in the leukocyte line, an increase in the differentiation rate from the stem cell compartment into the leukocyte line, and the rate of apoptosis in the stem cell compartment. Our model system is particularly sensitive to changes in stem cell apoptosis rates, suggesting that changes in the numbers of proliferating stem cells may be important in generating PCML.     

Familial neurofibromatosis and juvenile chronic myelogenous leukemia

Summary Two male children with familial neurofibromatosis were observed to develop juvenile chronic myelogenous leukemia. These two cases add to previous reports which have described an increased incidence of non-lymphocytic leukemia in patients with neurofibromatosis. In particular, the rare entity juvenile chronic myelogenous leukemia would appear to be the form of non-lymphocytic leukemia that has a definite association with familial neurofibromatosis.     

Abnormalities of the erythrocyte membrane in chronic myelogenous leukemia

Chronic myelogenous leukemia (CML) is a hematologic malignancy characterized by excessive growth of myeloid cells and their progenitors. The proportion of spectrin dimers compared to tetramers extracted from membranes at 4 degrees C, under low ionic strength conditions, increased in CML erythrocytes. These also displayed abnormal thermal sensitivity (between 45 and 46 instead of 49 degrees C). Crosslinking with the bifunctional reagent, dimethyl adipimidate (8.6 A) showed significant organizational modification of not only spectrin, but other cytoskeletal components such as ankyrin, bands 4.2 and 5. Enhanced concanavalin A (Con-A) agglutinability of CML erythrocytes also suggests altered topographic distribution of a functionally important membrane protein, band 3. The anion transport activities of erythrocytes from patients with CML and normal donors were comparable. In CML erythrocytes, significant reduction in the number of ankyrin-binding sites, present in the cytoplasmic domain of band 3, may lead to partial loss of cytoskeletal anchorage to the bilayer and account for their increased Con-A agglutinability and heat sensitivity and may lead to their premature removal from the circulation.     

A new case of chronic myelogenous leukemia with 14q+ marker and review of the literature

We report a new case of Ph 1 positive chronic myelogenous leukemia (CML) with 14q+ marker shown during chronic phase (CP) and subsequently in blastic crisis (BC). After a review of the literature, we discuss the biological significance of 14q+ marker in developing lymphoid cellular differentiation, during evolution of CML, that remains still unclear. Besides, we also discuss the prognostic value of this change, concluding that a larger number of cases may clarify this question, as also the unresponsivity to chemotherapy of the patient studies so far, may not be related to 14q+ marker.     

A new variant translocation (19q plus, 22q minus) in chronic myelocytic leukemia

A translocation between chromosome 19 and chromosome 22 was found in one out of nine patients with CML. All the remaining eight patients demonstrated a translocation between chromosomes 9 and 22. The clinical pattern of the disease was similar in the patient with the translocation between chromosomes 19 and 22 and in the other CML patients. Thus the presence of the Ph¹ chromosome appears to be more important for the course and pattern of the disease than the location of the translocated fragment.     

Abnormalities in erythrocyte membrane band 3 in chronic myelogenous leukemia

The anion transport activities of erythrocytes from patients with chronic myelogenous leukemia (CML) and normal donors were comparable. In CML erythrocytes, significant reduction in the number of ankyrin-binding sites, present in the cytoplasmic domain of band 3, may lead to partial loss of cytoskeletal anchorage to the bilayer and account for their increased Con-A agglutinability and heat-sensitivity (Basu, J., Kundu, M., Rakshit, M.M. and Chakrabarti, P. (1988) Biochim. Biophys. Acta 945, 121-126).     

Visual loss as initial presentation of chronic myelogenous leukemia

A previously healthy 17-year old girl presented with sudden visual loss in both eyes. Visual acuity on the right eye was 0.3 and on the left eye 0.1. Fundoscopic examination showed bilateral optic disc edema, retinal venous tortuousity and dilatation, retinal blot and flame-shaped hemorrhages, Roth spots and on the left eye dark blot preretinal hemorrhage covering the fovea. Laboratory evaluation showed white blood cell count of 455 x 10(9) L. Bone marrow biopsy confirmed the diagnosis of chronic myelogenous leukemia. Chemotherapy was initiated and led to the improvement of visual acuity. Fundus changes had resolved except for the preretinal hemorrhage on left eye which decreased in size. Preretinal hemorrhage in fovea caused maculopathy on the left eye. Three months after admisson visual acuity was 1.0 on the right eye and 0.3 on the left eye. Leukemia should always be included in the differential diagnosis of optic disc edema and retinal hemorrhages.     

Contribution to the study of periodic chronic myelogenous leukemia

The period (in the order of 40 to 80 days) in periodic chronic myelogenous leukemia (PCML) oscillations is quite long compared with the duration of the cell cycle of the hematopoietic stem cells from which the oscillations are presumed to originate (in the order of one or two days). Our objective is to understand the origin of these long-period oscillations using a G0 model for stem cell dynamics. We determine the local stability conditions and show under what conditions the Hopf bifurcation may occur. We interpret the role of each parameter in the loss of stability, and then examine a simpler model to try to deduce possible changes at the stem-cell level that might be responsible for the characteristics PCML.