Y loss in leukemia

2001-01-01   Daniel L. Van Dyke 

1.FACMG, Cytogenetics Laboratory, Mayo Clinic, USA

Clinics and Pathology


-Y is frenquently observed in myeloproliferative diseases (MPD), myelodysplasic syndromes (MDS), acute myeloid leukemias (AML), and can also be seen in lymphoproliferations


In CML with t(9;22) and in AML with a t(8;21), loss of the Y chromosome tends to occurs at a younger age than in the general population


  • Partial or complete reappearance of the Y chromosome has been described in several cases of AML in remission. In most or all of these AML cases, the 45,X,-Y cell population represented 80-100% of pre-remission metaphases. These observations support the interpretation that the leukemia cell karyotype is 45,X,-Y.
  • In MDS, the proportion of -Y cells has been observed to increase, decrease, remain stable, or fluctuate up and down on follow-up studies.
  • In four cases of Hodgkin disease, simultaneous fluorescence immunophenotyping and FISH showed that the -Y cell population was probably independent of the Hodgkin disease in at least two of the patients. It is notable that the -Y cells represented fewer than 10-15% of the metaphase cells in all four cases.
  • Cytology

    no known association


    In AML, a 45,X,-Y karyotype is believed to have an intermediate prognosis. In MDS, the prognosis appears to be neutral or favorable. There are insufficient data for MPD or lymphoproliferative disease


    Cytogenetics morphological

  • In PHA-stimulated lymphocyte karyotype studies of males, about 2% have one or more cells with loss of the Y chromosome. Cells with -Y are observed more often in males over age 55 than in younger males. In all age groups, the proportion of -Y cells is usually under 10%.
  • The pattern of Y loss is more striking in bone marrow aspirate karyotype studies. Here, clonal Y chromosome loss as a sole abnormality in the karyotype is a common finding. A 45,X,-Y karyotype is observed in about 6% of bone marrow karyotype studies from males, and it represents 15-20% of abnormal karyotypes.
  • The frequency of -Y cells increases with advancing age and is significantly greater in cases with MDS, MPD, AML, or lymphoproliferative disease than in subjects who have no evidence of disease. Subjects with no evidence of disease rarely exhibit more than 75% of cells with 45,X,-Y. Thus, if fewer than 75% of metaphase cells are -Y, the disease association is uncertain. However, if 75-100% of metaphase cells are -Y, the karyotype probably is disease-associated, even in older men.
  • Chromosome rearrangements involving the Y chromosome are rare in cancer and leukemia. Loss of the Y chromosome, in contrast, is a common secondary change in cancer cells and in a few leukemias (see below).
  • Additional anomalies

    In association with t(9;22) in CML and with t(8;21) in FAB-M2 AML, loss of the Y chromosome is generally considered a secondary event of no added clinical significance.

    Genes Involved and Proteins

    genes involved, if any, are unknown


    Pubmed IDLast YearTitleAuthors
    13846661992Loss of the Y chromosome from normal and neoplastic bone marrows. United Kingdom Cancer Cytogenetics Group (UKCCG).
    69858281980Chromosomes and causation of human cancer and leukemia. XXXV. The missing Y in acute non-lymphocytic leukemia (ANLL).Abe S et al
    80763561994Loss of Y chromosome. An age-related event or a cytogenetic marker of a malignant clone?Abeliovich D et al
    38593631985Loss of the Y chromosome in acute myelogenous leukemia: a report of 13 patients.Holmes RI et al
    75304821994Y chromosome loss in chronic myeloid leukemia detected in both normal and malignant cells by interphase fluorescence in situ hybridization.Kirk JA et al
    23397031990The frequency of aneuploidy in cultured lymphocytes is correlated with age and gender but not with reproductive history.Nowinski GP et al
    41169081972Age-associated aneuploidy: loss of Y chromosome from human bone marrow cells with aging.Pierre RV et al
    81117381994X and Y chromosome loss as sole abnormality in acute non-lymphocytic leukemia (ANLL).Riske CB et al
    111106762000Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study.Slovak ML et al
    77891811995Clarification of dubious karyotypes in Hodgkin's disease by simultaneous fluorescence immunophenotyping and interphase cytogenetics (FICTION).Weber-Matthiesen K et al
    105645812000Clinical significance of Y chromosome loss in hematologic disease.Wiktor A et al



    Loss of the Y chromosome from individual metaphases is common in metaphase cells from both PHA-stimulated lymphocytes and spontaneously dividing bone marrow cells. The frequency of Y loss is greater in older men, and the size of the 45,X,-Y cell population probably increases gradually with advancing age. (In females, a corollary loss of one X chromosome also occurs with advancing age.) This natural phenomenon challenges our ability to distinguish between a normal and a disease-associated 45,X,-Y clone.


    Daniel L. Van Dyke

    Y loss in leukemia

    Atlas Genet Cytogenet Oncol Haematol. 2001-01-01

    Online version: http://atlasgeneticsoncology.org/haematological/1089/y-loss-in-leukemia

    Historical Card

    1999-01-01 Y loss in leukemia by  François Desangles