Clonal remissions in acute myeloid leukaemia are commonly associated with features of trilineage myelodysplasia during remission. 1993

S N Jowitt, and J A Liu Yin, and M J Saunders, and G S Lucas
Department of Haematology, Manchester Royal Infirmary.

Clonal haemopoiesis has previously been demonstrated in some 30% of patients in remission of acute myeloid leukaemia (AML). Whilst a 'clonal remission' in many such patients may represent a skewed X-chromosome inactivation pattern in haemopoietic cells, its relationship to an underlying preleukaemic state remains uncertain. We therefore analysed the clonal status of 48 female patients in remission of AML using X-chromosome linked restriction fragment length polymorphisms (RFLPs) within the X-linked PGK and HPRT genes and the DXS255 (M27 beta) locus, and carried out in conjunction a detailed study of the morphological and karyotypic features of the patients' bone marrows. During remission, 35 patients (73%) with AML demonstrated nonclonal haemopoiesis, and their bone marrows were morphologically normal. Remission haemopoietic tissue in nine cases (19%) showed a skewed X-chromosome inactivation pattern and remission bone marrows in these patients had features of trilineage myelodysplasia (TMDS), with seven having similar features at presentation. Analysis of constitutional DNA showed a non-clonal pattern in seven of these patients, but was unsuccessful in two cases. These nine patients with post-chemotherapy TMDS were considered to have true clonal haemopoiesis. Four patients (8%) with a skewed X-chromosome inactivation pattern had normal remission bone marrows. Analysis of constitutional DNA showed a skewed pattern in two of these patients, but was unsuccessful in two cases. Cytogenetic investigation during remission in the nine patients with TMDS showed a normal karyotype in four cases and the acquisition of new karyotypic abnormalities in three cases. In contrast, 10 female patients in remission of de novo acute lymphoblastic leukaemia (ALL) were shown to have non-clonal haemopoiesis. We conclude that the majority of patients with AML who achieve remission after cytoreductive chemotherapy have non-clonal haemopoiesis, and when clonal remissions are observed these are commonly associated with the development of trilineage myelodysplasia in the bone marrow, with or without karyotypic abnormalities. True clonal remission in association with morphologically normal haemopoiesis is a rare entity, the significance and frequency of which remain uncertain.

UI MeSH Term Description Entries
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009190 Myelodysplastic Syndromes Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA. Dysmyelopoietic Syndromes,Hematopoetic Myelodysplasia,Dysmyelopoietic Syndrome,Hematopoetic Myelodysplasias,Myelodysplasia, Hematopoetic,Myelodysplasias, Hematopoetic,Myelodysplastic Syndrome,Syndrome, Dysmyelopoietic,Syndrome, Myelodysplastic,Syndromes, Dysmyelopoietic,Syndromes, Myelodysplastic
D012074 Remission Induction Therapeutic act or process that initiates a response to a complete or partial remission level. Induction of Remission,Induction, Remission,Inductions, Remission,Remission Inductions
D012150 Polymorphism, Restriction Fragment Length Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment. RFLP,Restriction Fragment Length Polymorphism,RFLPs,Restriction Fragment Length Polymorphisms
D001853 Bone Marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Marrow,Red Marrow,Yellow Marrow,Marrow, Bone,Marrow, Red,Marrow, Yellow
D004303 Dosage Compensation, Genetic Genetic mechanisms that allow GENES to be expressed at a similar level irrespective of their GENE DOSAGE. This term is usually used in discussing genes that lie on the SEX CHROMOSOMES. Because the sex chromosomes are only partially homologous, there is a different copy number, i.e., dosage, of these genes in males vs. females. In DROSOPHILA, dosage compensation is accomplished by hypertranscription of genes located on the X CHROMOSOME. In mammals, dosage compensation of X chromosome genes is accomplished by random X CHROMOSOME INACTIVATION of one of the two X chromosomes in the female. Dosage Compensation (Genetics),Gene Dosage Compensation,Hypertranscription, X-Chromosome,X-Chromosome Hypertranscription,Compensation, Dosage (Genetics),Compensation, Gene Dosage,Compensation, Genetic Dosage,Dosage Compensation, Gene,Gene Dosage Compensations,Genetic Dosage Compensation,Genetic Dosage Compensations,Hypertranscription, X Chromosome,X Chromosome Hypertranscription
D005260 Female Females
D006410 Hematopoiesis The development and formation of various types of BLOOD CELLS. Hematopoiesis can take place in the BONE MARROW (medullary) or outside the bone marrow (HEMATOPOIESIS, EXTRAMEDULLARY). Hematopoiesis, Medullary,Haematopoiesis,Medullary Hematopoiesis
D006412 Hematopoietic Stem Cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Colony-Forming Units, Hematopoietic,Progenitor Cells, Hematopoietic,Stem Cells, Hematopoietic,Hematopoietic Progenitor Cells,Cell, Hematopoietic Progenitor,Cell, Hematopoietic Stem,Cells, Hematopoietic Progenitor,Cells, Hematopoietic Stem,Colony Forming Units, Hematopoietic,Colony-Forming Unit, Hematopoietic,Hematopoietic Colony-Forming Unit,Hematopoietic Colony-Forming Units,Hematopoietic Progenitor Cell,Hematopoietic Stem Cell,Progenitor Cell, Hematopoietic,Stem Cell, Hematopoietic,Unit, Hematopoietic Colony-Forming,Units, Hematopoietic Colony-Forming
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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