Isochromosome (17q) in Philadelphia chromosome (Ph1)-negative juvenile chronic myelocytic leukemia

A dicentric isochromosome of the long arm of one chromosome #17 was the only abnormality present in a 12-year-old boy with Philadelphia chromosome (Ph¹)-negative juvenile chronic myelocytic leukemia. This association does not seem to have been reported in the literature. It is postulated that the finding of an isochromosome (17q) may also have a negative prognostic value in the Ph¹-negative type of chronic myelogenous leukemia.     

Two cases of acute myeloblastic leukemia (M2 type) with karyotypes 45X,-X,t(6;8)(q27;q22),inv(9) and 46,XY,t(8;21)(q22;q22),del(9)(q22)

Two patients with acute myelogenous leukemia (AML) are described. The first case is that of a patient with AML who had a low leukocyte alkaline phosphatase level associated with a variant (6;8)(q27;q22) translocation, coupled with loss of an X chromosome in bone marrow and unstimulated blood cells. The second case is that of an AML patient in whom the karyotype of the leukemic cells at the time of diagnosis was 46,XY,t(8;21)(q22;q22),del(9)(q22); at relapse, the patient acquired an additional chromosome #19. The lack of involvement of chromosome #21 in the first case, as well as the occurrence of an abnormality of chromosome #9, in addition to the t(8q-;21q+) in the second case are discussed with reference to the character of the possible specific chromosomal events in patients with type M2 AML.     

del(2)(p23): a new recurrent abnormality in acute myeloid leukemia

In two patients with acute myeloid leukemia, we found a new chromosome abnormality: del(2)(p23) which was detected in 13% and 50% of studied bone marrow cells, respectively. In patient one, del(2p) was an additional abnormality to t(8;21), while patient two had del(2p) as the sole abnormality. Based on our observation and a review of the literature we propose that del(2p) is a new recurrent chromosome abnormality for acute myeloid leukemia.     

Chromosome abnormalities in acute lymphoblastic leukemia

Less information is available on the cytogenetic abnormalities in marrow cells of patients with acute lymphoblastic leukemia (ALL) than on abnormalities in acute nonlymphocytic leukemia (ANLL); nonetheless, some patterns of karyotypic change in ALL are evident. Even with banding, about 50% of patients appear to have a normal karyotype. The modal chromosome number tends to be higher in ALL than in ANLL. Every patient with B-cell ALL has had an abnormality of one chromosome No. 14 that involved the translocation of material to the end of the long arm. Among seven reported cases, the translocation was from 8q in three patients and 11q in one. Cells with a haploid or near-haploid (24–35) chromosome number have been reported in five patients with ALL and in four patients in a lymphoid blast crisis of chronic myelogenous leukemia. The karyotype in the four ALL patients whose cells were analyzed with banding was remarkably consistent. All patients had the haploid number, usually with both sex chromosomes, plus an additional No. 10, 18, and 21. Evolution of the karyotype, which occurs in the leukemic cells of about 50% of patients, involves cells of patients who had an initially normal or an initially abnormal karyotype. The evidence regarding a correlation between the presence of an abnormal clone prior to treatment and response to treatment is contradictory at present. Some chromosome abnormalities, such as the presence of a Philadelphia (Ph¹) chromosome, a 14q+ chromosome, or a haploid clone, are associated with a relatively short survival.     

Diagnostic and prognostic significance of chromosome abnormalities in acute nonlymphocytic leukemia

Chromosome abnormalities in acute nonlymphocytic leukemia (ANLL) are of diagnostic and prognostic importance. The presence of an abnormality in ANLL patients predicts an unfavorable course; the prediction is particularly significant for acute myelocytic leukemia. The occurrence of a t(15;17) assists in the diagnosis of “microgranular” acute promyelocytic leukemia; transmission electron microscopy can aid in confirming this diagnosis. The presence of a chromosome abnormality in previously treated malignant lymphoma patients with undiagnosed cytopenia supports a diagnosis of preleukemia. The presence of a chromosome abnormality in patients with the hypereosinophilic syndrome might identify the subset of patients who have a neoplastic disease.     

Ph-positive CML in a family with a constitutional Robertsonian translocation 14;15

A patient with CML in chronic phase was admitted to our center for bone marrow transplantation. Cytogenetic analysis of bone marrow cells revealed a Ph chromosome due to a standard t(9;22) and a Robertsonian t(14;15). This Robertsonian translocation was also found in PHA-stimulated lymphocytes of the patient's sister, the donor of the bone marrow. A chromosome study of the whole family proved the constitutional character of the t(14;15) abnormality and showed that it was inherited from the father's side. All family members were phenotypically normal with normal mental status. Female carriers of the t(14;15), as well as wives of male carriers, had a high incidence of miscarriages and early death of their offspring. The occurrence of Ph-positive CML in a patient with a Robertsonian t(14;15) might indicate increased risk for the development of leukemia in patients with this constitutional chromosome abnormality. This assumption however, is limited by the rarity of the Robertsonian translocations.     

Chromosomal evidence of a common stem cell in acute lymphoblastic leukemia and chronic granulocytic leukemia

A patient with acute lymphoblastic leukemia (ALL) was found, at the time of diagnosis, to have an unusual Philadelphia chromosome (Ph¹) with a satellite marker. The disease evolved into the chronic phase of chronic granulocytic leukemia (CGL), with persistance of the marker. Two months later, the patient died of ALL.     

Acute myelogenous leukemia and thrombocythemia associated with an abnormality of chromosome No. 3

The association of thrombocythemia with acute myelogenous leukemia (AML) is unusual. A patient with markedly increased platelet counts in association with abnormal megakaryocytes was diagnosed as having AML. In addition a karyotypic abnormality involving a translocation of the long arm of a No. 3 chromosome was identified by Q-banding techniques. The translocation involved the other chromosome No. 3 [ins (3;3) (q26;q21q26)]. A specific structural rearrangement in human chromosomes in AML may be associated with abnormal megakaryocytes and increased platelets.     

"Masked" Ph1 chromosome in a complex three-way translocation

A patient with myelofibrosis was found to have a 46,XX,del(1)(q24),del(11)(p11),-22,+mar karyotype in unstimulated peripheral blood (PB) and spleen cells. On detailed cytogenetic examination it was determined that this patient had an apparently "masked" Ph1 chromosome contained in a complex three-way translocation. Since phytohemagglutinin (PHA)-stimulated PB and spleen cells were essentially normal, the masked Ph1 chromosome was assumed to be an acquired cytogenetic abnormality. The portion missing from the masked Ph1 chromosome was apparently translocated onto del(1). Thus, the detailed karyotype was 46,XX,t(1;11;22)(q24;p11;q11 or q12),t(1;22)(q24;q11 or q12). This complex rearrangement was present primarily in cells belonging to the granulocyte-macrophage cell lineage, whereas E-rosetting cells, and presumably T lymphocytes, had normal karyotypes.     

Translocation t(3;20) associated with thrombocythemia in Ph-positive CML

A patient with Philadelphia (Ph) chromosome positive chronic myelocytic leukemia is described who also developed an abnormality of chromosome #3, i.e., t(3;20)(p21;p13), in blast crisis. This abnormality may be connected with the advent thrombocythemia. The disease was a thrombopenia in the initial phase.     

Cytogenetic studies of hairy cell leukemia

Mononuclear cells from peripheral blood and spleen of four patients with hairy cell leukemia (HCL) were cultured for 1 to 10 days with and without phytohemagglutinin (PHA) stimulation. Blastogenesis and mitoses were not observed in the unstimulated cells cultured for up to 3 days. Prolonging the culture time of unstimulated cells to 7 days produced blastogenic response; a further increase in culture time to 10 days showed transformed cells but not mitoses. Poor PHA response was noted in the cultures stimulated for 3 days, but cells cultured for 7 days and then stimulated with PHA entered mitosis. Surface immunoglobulins were exhibited in 78–94% of the cells in the blood and spleen of patients. In addition, these cells had tartarate-resistant acid phosphatase and were able to phagocytize latex particles by which properties they were identified as hairy cell leukemia cells. Chromosome abnormalities were present in a proportion of cells of each patient, none of them, however, were clonal.     

dic(9; 20): A new recurrent chromosome abnormality in adult acute lymphoblastic leukemia

Loss of chromosome 20 and rearrangement of the short arm of chromosome 9 were identified by banding analysis of three adult patients with acute lymphoblastic leukemia (ALL). The G-banding pattern suggested and identical deletion of 9p, but, also, an unbalanced translocation with chromosome 20 was taken into consideration. Dual-color chromosome painting with probes for chromosomes 9 and 20 revealed the presence of material from chromosome 20 at the short arm of the abnormal chromosome 9 in all three cases. Centromeric alpha-satellite DNA of both chromosome 9 and chromosome 20 was demonstrated by fluorescence in situ hybridization and indicated the presence of a dicentric chromosome. The hybridization of a YAC clone of the short arm of chromosome 20 proved that the dicentric chromosome contained the short arm of chromosome 20, which had been suspected from the G-banding pattern. Thus, the rearrangement was interpreted as dic(9; 20)(pl I;qi I . ? I). Because this was the sole chromosome abnormality in two patients, dic(9; 20) may be a primary chromosome aberration in ALL. In one case, a 9q⁺ chromosome derived from a Philadelphia (Ph) translocation was involved in the formation of the dicentric chromosome. Immunophenotyping revealed CD 1o⁺ B-cell precursor ALL in all three cases. Whereas the two patients in whom dic(9; 20) was the sole cytogenetically detectable change are in continuous complete remission for 10 and 45 months, respectively, the Ph⁺ patient relapsed with leukemia and died 8 months after diagnosis. © 1995 Wiley-Liss, Inc.     

Acquired idiopathic sideroblastic anemia: a new chromosomal abnormality

We describe two patients with acquired idiopathic sideroblastic anemia and a terminal deletion of chromosome No. 11. In spite of the marked chromosomal abnormality neither patient has developed acute leukemia.     

A recurring chromosome rearrangement, dic(16;22), in acute nonlymphocytic leukemia

A dicentric chromosome, dic(16;22), resulting in the loss of 16q and 22p was seen in bone marrow cells from two patients with acute myelomonocytic leukemia and one patient with a therapy-related myelodysplastic syndrome that evolved to leukemia. Review of the clinical findings and of the bone marrow morphology failed to reveal any distinctive features in common among these patients. The dic(16;22) may be a new, rare, recurring abnormality associated with malignant myeloid disorders.     

Significance of abnormalities involving chromosomal segment 11q22-25 in acute leukemia

Six hundred and thirty unselected cases of acute leukemia, with complete data regarding age, karyotype (with breakpoints), and the diagnosis according to the FAB classification, were available in the literature and from our unpublished cases for comparing the incidence of chromosomal abnormalities involving the long arm of chromosome #11 among age groups in acute nonlymphocytic leukemia (ANLL) and acute lymphocytic leukemia (ALL). A statistically highly significant difference (p less than 0.001) was observed between the incidence of ANLL cases with chromosome aberrations involving 11q22-25 in childhood (less than or equal to 15 years) versus that in adults (greater than 15 yr). This statistical difference was not only related to infant cases (less than or equal to 12 months), but also to cases of children over 1 year of age. The incidence of the 11q22-25 abnormality in childhood cases (greater than 1 yr to less than or equal to 15 yr) was statistically significant (0.025 less than p less than 0.05) when compared to the incidence in adult cases. The incidence of the 11q22-25 abnormality in infant cases was much higher when compared to that of older cases with either ANLL or ALL (p less than 0.001 in each leukemia). This trend was not observed in cases with the 11q11-21 abnormality and this may imply that the origin and meaning of the 11q11-21 abnormality may differ from that of the 11q22-25 abnormality. Twenty-three infants with acute leukemia (AL) with the 11q22-25 abnormality were available from previous reports and our unpublished case. The median ages of ANLL, ALL, and all AL cases were 16 weeks, 9 weeks, and 15 weeks, respectively. The tendency of the 11q22-25 abnormality to be common in infants with ANLL or ALL under 6 months of age may suggest that it has a close correlation with the origin(s) or mechanism(s) related to the occurrence of infant AL.     

Translocation t(1;3)(p36;q21) in malignant myeloid stem cell disorders

A t(1;3)(p36;q21) translocation was found in bone marrow samples of two patients with hematologic disorders. One patient had a myelodysplastic syndrome evolving into acute nonlymphocytic leukemia (ANLL) M1 and the second patient had ANLL-M6 secondary to treatment for Hodgkin's disease. Because myelodysplastic syndromes and secondary leukemia are stem cell disorders, the t(1;3)(p36;q21) appears to be a chromosome abnormality in malignant myeloid stem cells.     

Complex translocations between chromosomes #6, #9, #22, and #11 in a patient with chronic myelocytic leukemia: 46,XX,t(6;9;22;11)(p21;q34;q11;q13)

A case of chronic myelocytic leukemia with myelofibrosis has been reported. An abnormal clone with a rearrangement of four chromosomes: 46,XX,t(6;9;22;11)[p21;q34;q11;q13] was observed. The possible significance of this chromosome abnormality is discussed.     

Myelodysplasia progressing to acute myeloblastic leukemia in an HTLV-III virus-positive homosexual man with AIDS-related complex

Myelodysplastic changes have recently been described in patients with the acquired immunodeficiency syndrome (AIDS). The authors report a patient with AIDS-related complex and myelodysplasia who rapidly progressed to acute myeloblastic leukemia. Infection with human T-cell lymphotropic virus type III (HTLV-III) was documented by culture and by serology. Chromosome studies showed monosomy of chromosome 7 and structural abnormality of the long arm of chromosome 3. The association of HTLV-III infection with myelodysplasia and acute myeloblastic leukemia may have been coincidental in this reported case, but it is also possible that the leukemia was secondary to the HTLV-III infection. Further investigation appears justified.     

Translocation (X;12)(p11;p13) as a sole abnormality in biphenotypic acute leukemia

A reciprocal t(X;12)(p11;p13) was found as the sole clonal abnormality in biphenotypic leukemia with myeloid and B-lymphoid differentiation. With fluorescence in situ hybridization analysis, the ETV6 gene (previously TEL) was found to be translocated intact to the derivative X chromosome; no MLL and BCR/ABL rearrangements were found. The patient achieved complete remission after induction chemotherapy. To our knowledge, this cytogenetic aberration has not been reported previously as a sole abnormality in hematological malignancies. Its presence may suggest an important role in the pathogenesis of biphenotypic leukemia.     

Oncogene mobility in a human leukemia line HL-60

HL-60, a cell line derived from a human promyelocytic leukemia, shows amplification of the oncogene c-myc. Chromosome aberrations reported in HL-60 include double minutes (DMs) and an abnormally banded region (ABR) on chromosome #8. A relationship between these chromosomal aberrations and amplification of c-myc DNA has been suggested. We report the localization by cytologic hybridization of amplified c-myc DNA to a marker chromosome, M3q+, in an early passage of HL-60. The localization of c-myc to an ABR on an 8q+ chromosome was confirmed in later passage clones. The most probable derivation of the M3q+ chromosome is t(5p;17q) with additional material associated with c-myc amplification inserted into 17q. This localization is of interest in light of the association between t(15:17) and promyelocytic leukemia. The results indicate that amplification and chromosome integration can occur at a site other than the native gene locus and at different integration sites in different lineages of the same tumor.