HISTORY OF CHRONIC MYELOID LEUKEMIA in 1900s

This post is about the history of one of the most important diseases in hematology, earlier known as leucocythemia, now chronic myeloid leukemia (CML).

In the last post we saw the various timelines in 1800s.

In this post we will see what happened in 1900’s in CML.

Increased use of stained blood films and later with the introduction of peroxidase stain defined the characteristic profile of the differential count in CML.

1900- Myeloblast was indentified as the precursor stage of granulocyte series. Before the identification of myeloblasts, all cases of acute leukemia and blasts in leucocythemia also were considered as lymphoid as these blasts were agranular.

1917- Dr.Gordon Ward, medical officer in British army, collected 247 cases of CML from world literature and studied the age, sex distribution, survival times of the patients.

Early 1920s- Basophilia and thrombocytosis were also recognized as specific for CML.

1920’s  and 1930’s-  There were lot of discussions on the pathophysiology of CML.

However, Virchow perception was it might be neoplastic because of the persistent, progressive and eventually fatal course.

1924- Minot et al, reported on 166 cases over a 10-year period and devised a statistical prediction of the probability of survival and of the subsequent ‘general ability’ of a patient with CML.

1931- Hoffman and Craver assessed 82 cases seen at the Memorial Hospital in New York, trying to assess the efficacy of radiation therapy.

1947- The granulocytes in CML had abnormally low leucocyte alkaline phosphatase content. This was first noted in 1947 and was used to distinguish CML from leukemoid reaction.

1950’s-  There was lot of research into the chromosomal constitution of neoplastic cells

1953-The first edition of Whitby and Brittons’s, a  famous textbook on diseases of blood gave a detailed description  of clinical picture, marrow morphology.

The term blast crisis was not used, but they noted that myeloblasts in more numbers could be seen in the later stages of disease, and it was refractory to treatment.

1960- Nowell and Hungerford described a minute acrocentric chromosome in cells cultured from the blood of seven CML patients. The findings were soon confirmed by other people and it  came to known as Philadelphia chromosome. For over a decade, it was the only chromosomal marker discovered, which correlated with a specific neoplastic disease.

From Nowell and Hungerford's paper in 1960 identifying the Philadelphia chromosome. (From the Journal of the National Cancer Institute.)

1963- Lymphoblastic transformation of the disease was first described by Georges Mathe A, who was a French physician and oncologist, using Romanowsky stained smears.

1973- Initially they thought that there was partial deletion of the long arm of chromosome 22. Janet Rowley showed that the deleted portion was not lost but translocated to the distal end of chromosome 9.

Descriptions of breakpoint cluster regions on chromosome 22 and characterization of BCR-ABL fusion gene, which yields an abnormal protein having a constitutively active tyrosine kinase were further important discoveries.

The discovery of Philadelphia chromosome was of great importance in understanding the pathogenesis and molecular biology of CML and used to distinguish CML from other myeloprolifertaive neoplasms.

Since 1839 cases were described, from the gross appearance of blood, seeing unstained smears under microscope, then stained smears, followed by special stains, then cytogenetics, molecular studies including polymerase chain reaction (PCR), Real time PCR, IRMA( Imatinib Resistance Mutational Analysis) and so on. 

Treatment and also the survival  of the patients  improved with the discovery of philadelphia chromosome and after understanding the molecular biology of the disease.

References:

1.     The story of chronic myeloid leukaemia. British Journal of Haematology.2000:110; 2- 11

                                      

                                                                         Written by Dr.Priyavadhana