Involvement of the short arm of the derivative chromosome 9 in Philadelphia-positive acute lymphoblastic leukemia

Three Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) patients showed rearrangement of the short arm of the chromosome 9 involved in Ph formation. At diagnosis, blast cells were morphologically L2 and phenotypically B-cell precursors, as shown by common ALL antigen (CALLA), B1, B4 and HLA-DR positivity. Cytogenetically, they had in common the presence of cells with normal karyotypes, the Ph, involvement of band 9p13----p21, and loss of region 9p13----9pter. In our experience, involvement of the p arm of the derivative chromosome 9 in Ph+ leukemias is a very rare event found in ALLs only.     

Partial trisomy of the short arm of chromosome 18 due to inversion duplication and direct duplication

We report one patient with a de novo inversion duplication 18 (ptercen) and two cases of direct tandem duplication 18 (ptercen), one due to maternal inheritance and the other arising as mosaicism of unknown origin. The duplications are demonstrated by high resolution banding. They were verified by in situ hybridization with a paint specific for chromosome 18 and with DNA probe LI.84 specific for the centromere region of chromosome 18. FISH with the genomic DNA probe pHRR68 specific for 18p11.32 revealed a subtle deletion concomitantly involved in the case of inversion duplication 18p. The patients exhibit slight developmental delay/moderate mental retardation and only a few dysmorphic features. The literature on trisomy 18p is reviewed and the present cases are compared to it.     

Long arm deletion of chromosome no. 5 in a case of Philadelphia chromosome-positive chronic myelocytic leukemia

A 28-year-old woman with chronic myelocytic leukemia was shown to have a long arm deletion of chromosome No. 5 (5q?) in addition to a Philadelphia chromosome (Ph¹) in the leukemic cells. Banding analysis revealed an interstitial deletion, del(5) (q14q23) and a standard Ph¹ translocation, t(9;22) (q34;q11). Based at the present and 37 previously reported cases of the 5q? anomaly in various hematologic disorders, a deleted segment between bands 5q22 and 5q23 is proposed to be common to all of the cases so far studied.     

Direct transmission of a tandem duplication in the short arm of chromosome 8

A family is described in which a mother and her two children carry a tandem duplication of the short arm of chromosome 8. Their phenotypes are similar and characterised by distinct facial dysmorphism, small stature and mild mental retardation. This is one of the first cases of direct familial transmission of a partial duplication of an autosomal chromosome segment.     

Clonal chromosome aberrations in Philadelphia-negative cells from chronic myelocytic leukemia patients treated with imatinib mesylate: report of two cases

Imatinib mesylate (tested as STI571), an abl kinase inhibitor, induces sustained, complete hematologic and cytogenetic responses in chronic myelocytic leukemia (CML) patients; however, emergence of clonal chromosomal aberrations in Philadelphia-negative (Ph-) cells during treatment has been reported. We describe two CML patients in chronic phase who presented with complete cytogenetic responses during imatinib mesylate therapy but developed new clonal chromosomal rearrangements in Ph- cells. The first patient presented with a duplication of chromosome 1, dup(1)(q21q42), and the second showed two new clonal aberrations consisting of inv(1)(q12q32) and del(7)(q22) in the same clone.     

Interstitial duplication of the short arm of chromosome 1 in a newborn with congenital heart disease and multiple malformations

Interstitial duplications of chromosomes 1p are rare, with only 14 cases previously reported in the literature, and those have not revealed a unique syndrome. The phenotypes include multiple congenital abnormalities and both intra- and extra-uterine growth retardation. In general, the patients do poorly and do not survive beyond the age of several months. We report a newborn male with karyotype 46, XY, inv dup(1)(qter--> p34.3::p34.3-->p32.3::34.3-->pter) with multiple congenital abnormalities including congenital heart disease and co-existing portal and pulmonary hypertension. The chromosome 1 origin of the extra material was confirmed with fluorescent in situ hybridization (FISH). Review of the GDB [Human Genome Database, 1990] reveals that the duplicated region includes the locus EDN2 that encodes endothelin-1, a potent vasoconstrictor, making genetic overdosage of this protein a likely etiology of the pulmonary hypertension. The diffuse abnormalities show effects in multiple cell lines and suggest that this region of chromosome 1p could be involved in determining cell migration and/or differentiation during organogenesis.     

Variant Philadelphia chromosome translocations in two patients with chronic myelogenous leukemia

Two patients with chronic myelogenous leukemia and new variant Philadelphia chromosome translocations are reported. In one case, a 41-year-old male, a 10;22 translocation was found in all bone marrow cells examined. Furthermore, the Y chromosome was missing in 90% of the analyzed metaphase cells. In the second patient, a 22-year-old male, all the marrow cells contained a complex rearrangement involving chromosomes No. 2, 9, and 22.     

Interstitial duplication of the short arm of chromosome 1 in a newborn with congenital heart disease and multiple malformations*

Interstitial duplications of chromosomes 1p are rare, with only 14 cases previously reported in the literature, and those have not revealed a unique syndrome. The phenotypes include multiple congenital abnormalities and both intra‐ and extra‐uterine growth retardation. In general, the patients do poorly and do not survive beyond the age of several months. We report a newborn male with karyotype 46, XY, inv dup(1)(qter→ p34.3::p34.3→p32.3::34.3→pter) with multiple congenital abnormalities including congenital heart disease and co‐existing portal and pulmonary hypertension. The chromosome 1 origin of the extra material was confirmed with fluorescent in situ hybridization (FISH). Review of the GDB [Human Genome Database, 1990 ] reveals that the duplicated region includes the locus EDN2 that encodes endothelin‐1, a potent vasoconstrictor, making genetic overdosage of this protein a likely etiology of the pulmonary hypertension. The diffuse abnormalities show effects in multiple cell lines and suggest that this region of chromosome 1p could be involved in determining cell migration and/or differentiation during organogenesis. © 2001 Wiley‐Liss, Inc.     

De novo inverted tandem duplication of the short arm of chromosome 12 in a patient with microblepharon

We present a patient with a de novo inverted duplication of nearly the entire short arm of chromosome 12 [inv dup(12)(p13.3p12)], which was characterized using GTG‐banding and spectral karyotyping. The patient was noted to have microblepharon, which has not been previously described in children with a similar chromosomal rearrangement. This patient represents one of the few examples of complete and pure trisomy 12p due to inverted duplication of the short arm of chromosome 12 and expands the clinical spectrum. © 2001 Wiley‐Liss, Inc.     

Ring chromosome 12 resulting from nonrandom telomeric associations with the short arm of chromosome 15 in a cerebellar astrocytoma

Ring chromosome 12 was found in an untreated cerebellar astrocytoma apparently resulting from nonrandom telomeric associations involving the short arm of chromosome 15, and both the long and short arms of chromosome 12. The clonal nonrandom telomeric associations of 15p to both ends of the chromosome 12 were transitory, but appear to be the precursor lesion in the evolution to ring chromosome 12 in this tumor. A multistep process in the formation of a ring chromosome resulting from nonrandom telomeric associations to both telomeres is illustrated. © 1993 Wiley-Liss, Inc.     

Interstitial deletion of the short arm of chromosome 3 as a primary chromosome abnormality in carcinomas of the breast

Interstitial deletions of the short arm of chromosome 3 were found in short-term cultures of five breast carcinomas (of 41 breast cancers with clonal aberrations analyzed by us during the same period). They were the only clonal structural change in three tumors; in the remaining two, the clone with 3p– coexisted with seemingly unrelated clones that had other structural and numerical aberrations. The deletions were identical, del(3)(p12p14), in four cases. The fifth tumor seemed to have a smaller deletion, interpreted as del(3)(p13p14). Our findings constitute karyotypic evidence that 3p deletions are relatively common in breast carcinomas and concur with the molecular genetic detection of loss of heterozygosity in this chromosome arm. The fact that the deletions were found as solitary changes indicates that loss of genetic information from 3p loci is an early, possibly primary, event in tumorigenesis. © 1993 Wiley-Liss, Inc.     

Lymphoblastic leukemia with lymphomatous features associated with abnormalities of the short arm of chromosome 9

Patients with acute lymphoblastic leukemia (ALL) who present with bulky disease of the lymph nodes, spleen, or mediastinum--so-called "lymphomatous ALL"--appear to represent a distinct subgroup among patients with ALL of T-cell lineage who have different clinical findings, but the biologic basis for these differences is not known. While studying 65 patients with lymphoblastic leukemia whose karyotype was determined at diagnosis, we compared the findings in 8 patients with lymphomatous ALL and 57 patients whose presentations were more typical of ALL. Six patients with lymphomatous ALL had karyotypic abnormalities leading to loss of bands p21-p22 on the short arm of chromosome 9. The mechanisms varied and included deletions, unbalanced translocations, or loss of the entire chromosome. Only 1 of the 57 patients without lymphomatous ALL had an abnormality of chromosome 9 at diagnosis (P less than 0.001). These findings indicate that loss of chromosomal material in the region of 9p21-p22 is closely associated with lymphomatous ALL; by analogy with retinoblastoma, in which gene deletions are associated with an enzyme deficiency, this disease may be related to the loss of the enzyme methylthioadenosine phosphorylase, previously reported in some of these patients.     

Subtle abnormalities in the short arm of chromosome 11 in acute myeloid leukemia

A series of four patients with small deletions of the short arm of chromosome #11 is presented. In two of these patients, deletion of 11p was the sole karyotypic abnormality. When compared with similar reported cases an association with FAB type M4 is apparent. Such cases may often be undocumented, because the deletions can be subtle. One patient with erythroleukemia shows an inversion of chromosome #11 involving band 11p15. Because the patients' fetal hemoglobin (HbF) became raised during the course of the disease, it is postulated that the hemoglobin beta chain gene at 11p15 may have been disrupted.     

Evidence of a new chimeric bcr/c-abl mRNA in patients with chronic myelocytic leukemia and the Philadelphia chromosome

The hallmark of chronic myelocytic leukemia is the presence of the Philadelphia chromosome (Ph1). In recent studies, we obtained data that strongly suggested the involvement of an oncogene, c-abl, in this type of leukemia. This oncogene, normally located on chromosome 9, is translocated to chromosome 22 as a result of the Ph1 translocation. In addition, we identified a region on chromosome 22, the breakpoint cluster region (bcr), which contains the chromosomal breakpoint in all patients with chronic myelocytic leukemia who are positive for Ph1. Recent studies have suggested that the bcr is part of a gene that is truncated as a consequence of the Ph1 translocation. The deleted part of this gene could be replaced by c-abl sequences; to test this hypothesis we analyzed the RNA of five patients with chronic myelocytic leukemia. All five had chimeric bcr/c-abl messenger RNA, suggesting that the deleterious effects of this disease can be associated with an abnormal chimeric protein encoded by the bcr and the c-abl oncogene.     

Prenatal detection of de novo duplication of the short arm of chromosome 18 confirmed by fluorescence in situ hybridization (FISH)

We present a patient with developmental delay, minor anomalies, and duplication 18p confirmed by fluorescence in situ hybridization with whole chromosome 18 painting probe (Oncor p5218). Our observation confirms the findings of other investigators that duplication 18p is not associated with major malformations. Am. J. Med. Genet. 80:487–490, 1998. © 1998 Wiley-Liss, Inc.