慢性髓系白血病细胞遗传学检查的临床意义分析

目的　探讨慢性髓系白血病 (CML)患者细胞遗传学改变与疾病的诊断、分期、分险率分组之间的关系。材料与方法　 15 5例CML患者按《血液病诊断及疗效标准》及Sokal危险指数进行分期分组 ,骨髓短期培训常规G显带后进行核型分析。结果　 15 5例CML患者中 ,14 8例Ph(+) ,占 95 5 % ,Ph(- )患者 7例 (4 5 % ) ,其中 4例Ph(- ) /bcr -abl(+) ,3例Ph(- ) /bcr-abl(- )。慢性期患者中 2 1例 (15 6 % )发生附加染色体畸变 ,主要有 +8(5例 ) ,+Ph(4例 ) ,+19(2例 ) ,-Y(2例 ) ,1q - (2例 )等 ;附加染色体畸变率高危组 >中危组 >低危组。加速期和急变期患者中 14例 (70 % )有附加染色体数量和 /或结构异常。结论　慢性期CML是一组高度异质性疾病 ,附加染色体畸变频率与疾病的风险度正相关 ,是判断疾病预后的有用参数。加速期、急变期CML多伴有非随机的附加染色体异常 ,这些染色体的出现可作为预后评估的指标。     

Karyotype abnormalities and their clinical significance in blast crisis of chronic myeloid leukemia

We examined karyotypes and their prognostic significance in a series of 122 patients with chronic myeloid leukemia in blast crisis. Of 73 patients cytogenetically examined at the onset of blast crisis 63% had developed secondary cytogenetic abnormalities in addition to the Philadelphia chromosome. These newly emerging abnormalities included a double Philadelphia chromosome in 20 patients, a trisomy 8 in 17, and an isochromosome 17q in 11 patients. Development of such additional karyotypic abnormalities was significantly associated with a shorter median survival and less response to cytoreductive treatment and was significantly more common in nonlymphoid blast crisis than in the lymphoid-type blast crisis. Thus, assessment of karyotypes at the onset of chronic myeloid leukemia blast crisis appears to be of prognostic significance for both remission duration and survival.     

Prognosis in chronic myeloid leukemia]

The clinical course of patients with chronic myelogenous leukaemia (CML) is very heterogenous. Survival is determined by the timing of disease transformation. A patient's risk of transformation can be defined, but the time when it will occur can not be predicted. A number of features recorded at the time of diagnosis correlate significantly with survival and can serve as prognostic parameters. Conventional therapy has not achieved a substantial delay in the universally fatal outcome of the disease. Allogenic or syngenic bone marrow transplantation to individuals with CML is at present the only treatment with a curative potential.     

Cytogenetic follow-up in chronic myeloid leukemia

Twenty-six patients with Philadelphia chromosome (Ph¹)-positive chronic myeloid leukaemia have been followed up cytogenetically. Twelve patients were found to have chromosome abnormalities in addition to the Ph¹, either in the chronic phase or during progression of disease. The most common abnormality observed was an additional chromosome No. 19 although trisomy 8, a second Ph¹ and isochromosome 17 were also observed.     

Stem cell biomarkers in chronic myeloid leukemia

Chronic myeloid leukemia (CML) is a clonal multi-step myeloproliferative disease that is initially produced and ultimately sustained by a rare subpopulation of BCR-ABL+ cells with multi-lineage stem cell properties. These BCR-ABL+ CML stem cells are phenotypically similar to normal hematopoietic stem cells which are also maintained throughout the course of the disease at varying levels in different patients. Defining the unique properties of the leukemic stem cells that produce the chronic phase of CML has therefore had to rely heavily on access to samples from rare patients in which the stem cell compartment is dominated by leukemic elements. Here we review past and ongoing approaches using such samples to identify biologically and clinically relevant biomarkers of BCR-ABL+ stem cells that explain their unusual biology and that may help to design, or at least predict, improved treatment responses in CML patients. These studies are of particular interest in light of recent evidence that chronic phase CML stem cells are not only innately resistant to imatinib mesylate and other drugs that target the BCR-ABL oncoprotein, but are also genetically unstable.     

Variant Ph translocations in chronic myeloid leukemia

Variant translocations were found in eight of 142 consecutive patients with Ph-positive, chronic myeloid leukemia encountered in our laboratory during the last decade. Two patients had simple, two-way variant translocations: t(17;22)(p13;q11) and t(16;22)(q24;q11). Both of these patients had an additional translocation involving chromosomes #9: t(7;9)(q22;q34) and t(9;17)(q34;q21), respectively. Complex variant translocations were found in four cases: t(2;9;22)(p23q12;q34;q11), t(3;9;22)(p21;q34;q11), t(9;12;22)(q34;q13;q11q13), and t(13;17;22)(p11;p11q21;q11). In two cases, the only discernable cytogenetic aberration was del(22)(q11). A review of the chromosomal breakpoints involved in this series and in 185 cases of variant Ph translocations previously reported in the literature reveals that a disproportionately large number of breakpoints are located in light-staining regions of G-banded chromosomes. Furthermore, the breakpoints in simple variant translocations are more often located in terminal chromosomal regions, whereas, the breakpoints in complex translocations typically affect nonterminal bands. No obvious correlation was detected between variant Ph translocation breakpoints and either fragile sites, oncogene locations, or consistent chromosome breakpoints in other malignancies.     

Adrenal function in chronic myeloid leukemia]

Adrenal function was studied in patients with chronic myeloid leukaemia treated in the past or presently with Busulphan. Adrenocortical function was determined by means of 24-hour profile of 11-hydroxysteroids (11-OHCS) in plasma, and urinary 24-hour 17 hydrocorticosteroids (17-OHCS) and 17-ketosteroids (17-KS). The adrenomedullary function was determined measuring VMA level in 24-hour urine. In most patients normal 24-hour 11-OHCS profiles and 24-levels of 17-OHCS, 17-KS and VMA. Only in some cases these levels were raised. This rise was observed more frequently in patients with blastic crisis of myeloid leukaemia which may indicate that the adrenal reserve was maintained in these patients. The investigations failed to show that the disease itself or Busulphan treatment impaired adrenal function. The possibility of a direct effect of Busulphan on melanin metabolism in the organism is discussed.     

Complex Ph translocations in chronic myeloid leukemia

Monosomy for chromosome 5 or a portion of the long arm is a common finding in acute nonlymphocytic leukemia (ANLL) and myelodysplastic syndrome (MDS), especially when the disorder is therapy related [1,2]. If only a portion of chromosome 5 is missing, the loss is usually accomplished by interstitial deletion of various bands, most frequently q12-14 to q31-33 [3]. Occasionally monosomy for 5q is the result of a translocation between chromosome 5 and another chromosome, with the loss of the derivative chromosome that contains 5q. A previously described unbalanced translocation involves chromosome 7: [der(5)t(5;7)(q11.2;p11.2)] and appears to be a recurring abnormality in these disorders [4]. We report here one case of therapy related MDS, one case of MDS which may be therapy related, and two cases of MDS with another "variant" 5q - abnormality, namely a derivative chromosome 3 composed of most of the short arm of chromosome 5 and the long arm of chromosome 3: [der(3)t(3;5)(?p11;?p11)].     

Advances in the treatment of chronic myeloid leukemia

Fortunately radiation accidents are infrequent occurrences, but since they have the potential of large scale events like the nuclear accidents of Chernobyl and Fukushima, preparatory planning of the medical management of radiation accident victims is very important. Radiation accidents can result in different types of radiation exposure for which the diagnostic and therapeutic measures, as well as the outcomes, differ. The clinical course of acute radiation syndrome depends on the absorbed radiation dose and its distribution. Multi-organ-involvement and multi-organ-failure need be taken into account. The most vulnerable organ system to radiation exposure is the hematopoietic system. In addition to hematopoietic syndrome, radiation induced damage to the skin plays an important role in diagnostics and the treatment of radiation accident victims. The most important therapeutic principles with special reference to hematopoietic syndrome and cutaneous radiation syndrome are reviewed.     

Near-haploidy in a case of chronic myeloid leukemia

A case of Philadelphia chromosome positive chronic myeloid leukemia is reported in which the patient developed a near-haploid cell line during blast transformation. Although there was only one copy of most chromosomes, two copies of chromosomes 8, X, and 21 were present and the significance of this is discussed. It is postulated that a haploid event rather than chromosome loss was responsible for this. It was not associated with a particularly aggressive course of the disease. The relationship between the near-haploidy and cellular morphology is examined.     

15-LO在慢性髓系白血病中作用的研究进展

正白血病是一组高度异质性的造血系统恶性肿瘤,有一种或几种白细胞出现质和量的异常,并在骨髓和其它器官中广泛浸润,导致正常血细胞减少。白血病按照细胞类型的不同,分为髓系白血病和淋巴细胞白血病;按自然病程和细胞的成熟度分为急性白血病和慢性白血病。其中,慢性髓系白血病(chronic myeloid leukemia,CML)是造血干/祖细胞恶性增殖、分化和凋亡受阻的克隆性疾病,在成年白血     

Nuclear remodeling of telomeres in chronic myeloid leukemia

Chronic myeloid leukemia (CML) is a hematologic cancer characterized by the proliferation of myeloid cells and the translocation between chromosomes 9 and 22, [t(9;22)(q34.1;q11.2)]. At the chronic phase (CP), CML cells present longer telomeres than at the other clinical phases, display arm‐specific maintenance of individual telomere lengths, and are chromosomally stable. We asked whether an alteration of nuclear organization of telomeres, which is associated with genomic instability, occurs in CML cells at the CP. We used fluorescent in situ hybridization of telomeres combined with three‐dimensional (3D) quantification to study the nuclear telomeric architecture of CML cells at the CP. We found that cells can exhibit high telomere numbers, different telomere distributions, and alterations in peripheral or central nuclear location of telomeres. Also, we show that CML cells can be categorized in two groups according to the number of their telomere aggregates (TAs). We propose that the presence of high TAs in some samples is associated with the increased genomic instability and could be an indication of the clinical transitional phase. Also, alterations of nuclear organization of telomeres at the CP confirm that nuclear remodeling of telomeres can occur at an early clinical stage of a cancer. © 2013 Wiley Periodicals, Inc.     

Clinical morphology of chronic myeloid leukemia]

The morphological features of chronic myeloid leukemia at different stages of the disease were specified basing on the study of bone marrow punch biopsies of 239 patients, surgically removed spleens of 32 patients, marginal liver biopsies of 22 patients and 69 autopsies. It was found valid to distinguish two histological variants: granulocytic and granulocytic-megakaryocytic. It was shown that in the latter form of leukemia myelofibrosis, primarily of reticulin type, often tends to develop. The granulocytic-megakaryocytic variant and the diffuse myelofibrosis were found to be related to the morphological manifestations of unfavourable prognosis of chronic myeloid leukemia. The accumulation of blast cells in the central parts of bone marrow cavities, as revealed in the punch biopsies is the indication of the beginning of the blast transformation.     

Complex Ph1 translocation in chronic myeloid leukemia

This report describes a new case of chronic myeloid leukemia with an unusual Philadelphia chromosome translocation involving chromosomes No. 4,9, and 22; t(4,9,22) (q31;q34;q11).