Cytogenetic studies of haemopoietic colonies from patients with an initial diagnosis of acute lymphoblastic leukaemia.
For patients with an initial diagnosis of Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukaemia (ALL) and no documented history of Ph1-positive chronic myeloid leukaemia (CML), the cell of origin and extent of lineage involvement of the disease is often unclear. This is largely due to the fact that cytogenetic analysis of direct marrow preparations cannot distinguish between the presence of Ph1-positive myeloid metaphases and infiltration of the marrow with dividing Ph1-positive blasts. Cytogenetic analysis of cultured haemopoietic colonies allows more precise lineage assignment. We have used this approach to study five adult patients who presented with Ph1-positive ALL and subsequently showed a significant increase in normal metaphases (to 18-100% of all metaphases examined) following remission induction. In four of these five patients, some Ph1-positive erythroid and granulopoietic cells could be demonstrated. In the other, as in three patients with childhood ALL who presented with a Ph1-negative but cytogenetically abnormal clone, only chromosomally normal erythroid and granulopoietic progenitors were detected. Two Ph1-positive CML patients who entered a lymphoid blast crisis following a recognized chronic phase were also studied. In both of these latter two patients all erythroid and granulocyte-macrophage colonies analysed were Ph1-positive. These findings support the concept that patients presenting with Ph1-positive ALL comprise a heterogeneous group. In some cases the disease may arise in a restricted lymphopoietic cell not capable of myelopoietic differentiation. However, in others involvement of myeloid cells suggests these may be variant forms of CML in spite of an unusual initial response of the Ph1-positive clone to therapy.
Kalousek
D K
DK
Terry Fox Laboratory, B.C. Cancer Research Centre, Vancouver, B.C., Canada.
Dubé
I D
ID
Eaves
C J
CJ
Eaves
A C
AC
D000328:Adult; D001853:Bone Marrow / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000648:ultrastructure; D005260:Female; D006098:Granulocytes / Q000648:ultrastructure; D006412:Hematopoietic Stem Cells / Q000648:ultrastructure*; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D014410:Tumor Stem Cell Assay